Affinage

CAMP

Cathelicidin antimicrobial peptide · UniProt P49913

Round 2 corrected
Length
170 aa
Mass
19.3 kDa
Annotated
2026-04-28
130 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAMP encodes the sole human cathelicidin, hCAP-18, which is processed extracellularly by proteinase 3 in neutrophils—and by kallikrein serine proteases (KLK5/KLK7) in skin—to release the amphipathic α-helical peptide LL-37 that kills bacteria by forming toroidal pores in anionic membranes (PMID:11389039, PMID:12767238, PMID:17012259). Beyond direct antimicrobial activity, LL-37 functions as a multifaceted immunomodulator: it neutralizes LPS by competing with LBP for CD14 binding, recruits leukocytes via FPRL1/FPR2, activates the P2X7–NLRP3 inflammasome axis for IL-1β release, transports self-DNA and self-RNA into endosomes to trigger TLR7/TLR8/TLR9-mediated type I interferon production, delivers cGAMP intracellularly to activate STING-dependent antiviral responses, and promotes angiogenesis and wound re-epithelialization through FPRL1 on endothelial cells (PMID:11015447, PMID:12244186, PMID:23267025, PMID:17873860, PMID:19703986, PMID:35649354, PMID:12782669). CAMP transcription is induced by vitamin D via VDR downstream of TLR2/1 signaling and by HIF-1α recruited to the CAMP promoter through STAT3, linking innate immune sensing and metabolic cues to cathelicidin-dependent host defense against pathogens including Mycobacterium tuberculosis and uropathogenic E. coli (PMID:16497887, PMID:27633343, PMID:16751768). LL-37 also breaks innate tolerance to self-nucleic acids—serving as an autoantigen recognized by T cells in psoriasis—and drives pathological inflammation in psoriasis and rosacea through aberrant protease processing and TLR activation (PMID:25470744, PMID:17676051, PMID:31913271).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Identification of the C-terminal domain of CAP18 as the minimal LPS-binding and bactericidal module established that cathelicidins concentrate antimicrobial function in a short cationic α-helical segment whose integrity is essential for activity.

    Evidence Synthetic truncation variants tested in MIC assays against multiple bacterial species, with serum stability evaluation (rabbit CAP18)

    PMID:8109914 PMID:8313956

    Open questions at the time
    • Human LL-37 peptide not yet identified
    • Processing enzyme in vivo unknown
    • Mechanism of membrane killing unresolved
  2. 1995 High

    Cloning of the human CAMP gene revealed that LL-37 is the only human cathelicidin, with broad-spectrum antibacterial activity and LPS-neutralizing capacity that protects against endotoxemia in vivo, establishing a dual antimicrobial and anti-inflammatory role.

    Evidence cDNA cloning from bone marrow, synthetic LL-37 antimicrobial assays, LPS-binding assays, mouse endotoxemia survival model

    PMID:7529412 PMID:7649303 PMID:7890387

    Open questions at the time
    • In vivo processing enzyme unknown
    • Mechanism of LPS neutralization at receptor level unresolved
    • NMR structure of human LL-37 not yet determined
  3. 1996 High

    Complete genomic characterization placed CAMP at 3p21.3 with four exons and defined its granulocyte-restricted expression during myeloid differentiation, revealing that transcription peaks at the myelocyte stage while protein accumulates through terminal neutrophil maturation.

    Evidence FISH mapping, somatic cell hybrid PCR, Northern/Western blot of bone marrow differentiation stages, immunohistochemistry

    PMID:8681941 PMID:8946956 PMID:9850169

    Open questions at the time
    • Regulation of transcription beyond myeloid commitment unknown
    • Post-transcriptional storage mechanism not characterized
  4. 1998 High

    Structure-activity studies demonstrated that LL-37's antibacterial potency depends on anion-induced cooperative α-helical oligomerization, and identification of apolipoprotein A-I as a plasma scavenger explained why serum attenuates LL-37 activity.

    Evidence CD spectroscopy with anion titrations, MIC assays, affinity chromatography, SPR binding kinetics, anti-apoA-I blocking antibody

    PMID:9452503 PMID:9837875

    Open questions at the time
    • Oligomeric state and stoichiometry on bacterial membranes unknown
    • In vivo relevance of apoA-I scavenging during infection unresolved
  5. 2000 High

    Discovery that LL-37 is chemotactic for monocytes, neutrophils, and T cells via FPRL1/FPR2 receptor transformed understanding of cathelicidin from a simple antimicrobial to an immune cell recruiter bridging innate and adaptive immunity.

    Evidence Chemotaxis assays, Ca²⁺ mobilization in FPRL1-transfected HEK293 cells, cross-desensitization with FPRL1-specific agonists, expression in NK cells, γδ T cells, monocytes

    PMID:11015447 PMID:11049988

    Open questions at the time
    • Downstream FPRL1 signaling cascade not mapped
    • Relative contribution of chemotaxis vs. antimicrobial activity in vivo unknown
  6. 2001 High

    Identification of proteinase 3 as the specific extracellular processing enzyme for hCAP-18→LL-37 after neutrophil degranulation, combined with the mechanism of LPS neutralization via competitive blockade of LBP–CD14 interaction, defined the activation and anti-endotoxin pathways.

    Evidence Immunoelectron microscopy, selective protease inhibitor panel, LPS–CD14 binding competition, in vivo endotoxin model

    PMID:11389039 PMID:11544322

    Open questions at the time
    • Tissue-specific processing enzymes outside neutrophils unknown
    • Kinetics of proteinase 3 cleavage at infection sites not determined
  7. 2003 High

    LL-37 was shown to form toroidal pores in bacterial membranes (not barrel-stave or detergent-like), to promote angiogenesis and wound re-epithelialization via FPRL1 on endothelial cells, and to be required for skin repair—expanding its role from antimicrobial defense to tissue regeneration.

    Evidence Solid-state ¹⁵N/³¹P NMR in oriented bilayers, CAM angiogenesis assay, CRAMP-knockout mouse wound model, ex vivo human wound model with anti-LL-37 blocking antibody

    PMID:12603850 PMID:12767238 PMID:12782669

    Open questions at the time
    • Pore size and stoichiometry not resolved
    • Signaling pathway downstream of FPRL1 in endothelial cells not elucidated
  8. 2004 High

    LL-37 was found to directly activate the P2X7 receptor on monocytes to trigger caspase-1 and IL-1β release independently of autocrine ATP, establishing it as an endogenous danger signal coupling antimicrobial peptide release to inflammasome activation.

    Evidence P2X7 pharmacological inhibitors (oxidized ATP, KN04, KN62), apyrase control, IL-1β ELISA, caspase-1 assay in LPS-primed monocytes

    PMID:15067080

    Open questions at the time
    • Direct biophysical interaction between LL-37 and P2X7 not demonstrated
    • NLRP3 involvement not yet tested
  9. 2006 High

    A TLR2/1→VDR→CYP27B1→vitamin D→CAMP transcriptional axis was discovered in macrophages, causally linking vitamin D sufficiency to cathelicidin-dependent killing of intracellular M. tuberculosis; concurrently, CRAMP-knockout mice revealed cathelicidin's essential role in urinary tract defense, and kallikrein proteases were identified as skin-specific processing enzymes generating diverse cathelicidin peptide forms.

    Evidence TLR-stimulated macrophages with vitamin D measurements, siRNA knockdown of CAMP abolishing mycobacterial killing, CRAMP-KO UTI model, SCTE/SCCE siRNA and SPINK5-KO mice for skin processing

    PMID:16497887 PMID:16751768 PMID:17012259 PMID:17675463

    Open questions at the time
    • VDR binding site in CAMP promoter not mapped at nucleotide resolution in this work
    • Clinical vitamin D supplementation efficacy for TB unproven
  10. 2007 High

    LL-37 was discovered to break innate tolerance to self-DNA by condensing extracellular DNA into aggregates that resist degradation, delivering them into early endosomes of plasmacytoid DCs to activate TLR9 and drive type I IFN—establishing the mechanism for LL-37-mediated autoimmune amplification in psoriasis and linking aberrant cathelicidin processing to rosacea pathogenesis.

    Evidence pDC IFN-α assays, TLR9 reporter, confocal microscopy of LL-37–DNA endosomal uptake, gel retardation; Camp-KO mice for rosacea; MHC tetramer identification of LL-37-specific T cells in psoriasis patients

    PMID:17676051 PMID:17873860

    Open questions at the time
    • Structural basis of LL-37–DNA condensation unknown
    • Why some individuals develop autoimmune responses to LL-37 while others do not is unresolved
  11. 2008 High

    The three-dimensional NMR structure of LL-37 in lipid micelles revealed a curved helix-bend-helix amphipathic architecture with direct lipid contacts via aromatic and cationic residues, and defined KR-12 (residues 18–29) as the minimal bactericidal core—providing the first atomic-resolution template for the human cathelicidin.

    Evidence 3D triple-resonance NMR of ¹³C,¹⁵N-labeled LL-37, intermolecular NOEs with D8PG micelles, MIC assays of KR-12

    PMID:18818205

    Open questions at the time
    • No crystal structure of LL-37 in a membrane bilayer context
    • Oligomeric pore structure not resolved
  12. 2009 High

    Extension of the nucleic acid transport paradigm to self-RNA showed that LL-37–RNA complexes differentially activate TLR7 in pDCs and TLR8 in mDCs, broadening the mechanism of innate tolerance breaking beyond DNA to include RNA sensing.

    Evidence pDC/mDC stimulation assays, IFN-α/TNF-α ELISA, TLR7/TLR8 blocking antibodies and reporter assays, RNA protection assay, immunohistochemistry of psoriatic skin

    PMID:19703986

    Open questions at the time
    • Structural determinants governing LL-37 preference for RNA vs. DNA unknown
    • Relative contribution of TLR7 vs. TLR8 pathway in psoriasis not quantified
  13. 2012 High

    Two cytosolic sensing pathways were linked to LL-37: transport of self-DNA into monocytes activates the STING–TBK1 axis for type I IFN (TLR-independent), and LL-37 activates P2X7-dependent K⁺ efflux to trigger the NLRP3 inflammasome in macrophages, creating a feedforward loop with NETosis in lupus.

    Evidence siRNA knockdown of STING and TBK1, NLRP3 inhibitors, P2X7 inhibitors, potassium efflux measurement, lupus patient macrophages

    PMID:22927244 PMID:23267025

    Open questions at the time
    • How LL-37 escapes endosomes to deliver DNA to cytosolic STING unknown
    • Therapeutic targetability of the NET–LL-37–NLRP3 loop not tested
  14. 2014 High

    LL-37 was identified as a T-cell autoantigen in psoriasis, with LL-37-specific CD4⁺/CD8⁺ T cells infiltrating lesional skin and correlating with disease severity, definitively linking cathelicidin to adaptive autoimmunity.

    Evidence MHC-peptide tetramer staining, intracellular cytokine profiling, flow cytometry, skin biopsy immunohistochemistry, PASI correlation

    PMID:25470744

    Open questions at the time
    • HLA restriction elements for all LL-37 epitopes not fully defined
    • Whether LL-37-specific T cells are pathogenic drivers or bystanders not formally proven
  15. 2016 High

    Transcriptional regulation of CAMP was extended to a STAT3→HIF-1α axis (HIF-1α directly recruited to the CAMP promoter), and LL-37 was shown to activate MAVS→TBK1→AKT→IRF3→IFN-β signaling in keratinocytes when complexed with dsRNA, linking cathelicidin to cytosolic antiviral sensing beyond TLR pathways.

    Evidence ChIP showing HIF-1α at CAMP promoter, shRNA/inhibitor knockdowns, STAT3-mutant patient macrophages; MAVS-KO mice, siRNA in keratinocytes, psoriatic skin IFN-β gene signatures

    PMID:27438769 PMID:27633343

    Open questions at the time
    • Whether HIF-1α and VDR cooperate or act independently at the CAMP promoter not resolved
    • Relative contribution of MAVS vs. TLR pathways in skin inflammation not quantified
  16. 2018 High

    LL-37's receptor repertoire was expanded to include FPR2/ALX on platelets (mediating thrombus formation, confirmed in Fpr2/3-KO mice) and MrgX2 on mast cells (mediating degranulation via clathrin-dependent endocytosis), establishing LL-37 as a multi-receptor signaling ligand in hemostasis and allergy.

    Evidence FPR2/ALX inhibitor + Fpr2/3-KO mice for platelet aggregation/bleeding time; MrgX2 siRNA/overexpression, endocytosis inhibitors, confocal co-localization in mast cells

    PMID:30280189 PMID:30413433

    Open questions at the time
    • Structural basis of LL-37 promiscuity across GPCRs (FPRL1, FPR2, MrgX2) unknown
    • In vivo relevance of mast cell MrgX2 activation by LL-37 in disease settings not established
  17. 2022 High

    Discovery that LL-37 binds and transports cGAMP intracellularly to activate STING-dependent antiviral immunity added a cell-extrinsic second messenger delivery function, positioning cathelicidin as a carrier that bridges extracellular danger signals to cytosolic innate sensors.

    Evidence cGAMP-LL-37 binding assay, STING-KO cell IFN reporter, antiviral assay in vivo, LL-37 induction by vitamin D3/butyrate

    PMID:35649354

    Open questions at the time
    • Stoichiometry and affinity of cGAMP–LL-37 complex not determined
    • Whether other cathelicidins share cGAMP transport capacity unknown
    • Endosomal escape mechanism for cGAMP delivery to cytosolic STING not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of the LL-37 oligomeric pore in a membrane bilayer, the mechanism by which LL-37-cargo complexes escape endosomes to access cytosolic sensors (STING, MAVS), and whether the multiple receptor interactions (FPRL1, FPR2, P2X7, MrgX2, RAGE) operate cooperatively or in cell-type-specific isolation during infection and autoimmunity.
  • No high-resolution structure of LL-37 pore in a bilayer
  • Endosomal escape mechanism unknown
  • Integrated signaling model across multiple receptors lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0090729 toxin activity 5 GO:0098772 molecular function regulator activity 4 GO:0140104 molecular carrier activity 4 GO:0048018 receptor ligand activity 3
Localization
GO:0005576 extracellular region 5 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 13 R-HSA-162582 Signal Transduction 9 R-HSA-1643685 Disease 6 R-HSA-109582 Hemostasis 1
Partners
AGERAPOA1FPR2KLK5KLK7MRGPRX2P2X7RPRTN3

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The human CAMP gene (then called FALL39) encodes a cathelin-type precursor protein of 170 amino acids; the mature antibacterial peptide LL-37 is derived from the C-terminal domain (exon 4) after processing, and synthetic FALL-39/LL-37 has potent antibacterial activity against Gram-negative and Gram-positive bacteria. The gene is expressed in bone marrow and testis. cDNA cloning from bone marrow library, PCR, RNA blot, chemical synthesis and antimicrobial assay, CD spectroscopy Proceedings of the National Academy of Sciences of the United States of America High 7529412
1995 Human CAP18 (CAMP gene product) is expressed specifically in granulocytes; its C-terminal 37-amino-acid domain (CAP18(104-140), equivalent to LL-37) binds LPS, inhibits LPS-induced nitric oxide release from macrophages, inhibits LPS-induced tissue factor generation, and protects mice from LPS lethality. cDNA cloning from bone marrow library, Western blot with specific antiserum, synthetic peptide antimicrobial and LPS-binding assays, in vivo mouse endotoxemia model Infection and immunity High 7890387
1996 The FALL39/CAMP gene has four exons spanning ~1963 bp; exons 1–3 encode the signal sequence and cathelin region, while exon 4 encodes the mature LL-37 peptide. The gene is the only cathelicidin family member in the human genome. Dipeptidyl-peptidase I processing of synthetic FA-LL-37 yields mature LL-37, which is isolated from degranulating granulocytes. Genomic sequencing, exon mapping, anti-LL37 IgG immunolocalization in granulocytes, dipeptidyl-peptidase I processing, antibacterial assay European journal of biochemistry High 8681941
1996 The human CAP18 (HCAP18) gene maps to chromosome band 3p21.3, contains 4 exons spanning ~3 kb with ~700 bp upstream sequence, lacks typical TATA or CCAAT boxes, and is expressed specifically in granulocytes as shown by Western, Northern blot and RT-PCR. Genomic phage library cloning, somatic cell hybrid panel PCR mapping, fluorescence in situ hybridization (FISH), Northern blot, RT-PCR, Western blot, promoter mapping in COS7 cells FEBS letters High 8946956
1995 The solution structure of the active C-terminal domain of rabbit CAP18 (CAP18(106-137)) in 30% TFE determined by NMR is a complete, rigid amphipathic alpha-helix. In the presence of lipid A, CAP18(106-137) adopts at least three lipid A concentration-dependent helical conformations, and the cationic and hydrophobic groups segregate to interact with lipid A via coulombic and hydrophobic interactions. Circular dichroism (CD) spectroscopy, NMR spectroscopy in TFE, interaction studies with lipid A FEBS letters High 7649303
1997 The CAMP gene encoding LL-37 is not expressed in normal human skin keratinocytes but is strongly induced in keratinocytes during inflammatory skin disorders (psoriasis, atopic dermatitis, wound healing). In situ hybridization and immunohistochemistry localized the transcript and peptide to keratinocytes throughout inflamed epidermis, and fractions from psoriatic scales exhibited antibacterial activity. In situ hybridization, immunohistochemistry, Northern blot, antibacterial assay of psoriatic scale fractions The Journal of biological chemistry High 9182550
1998 The conformation-dependent antibacterial activity of LL-37 was established: LL-37 is disordered in water at low concentration but adopts a cooperative alpha-helical oligomeric structure induced by anions (HCO3−, SO4 2−, CF3CO2−) or increasing peptide concentration. The degree of alpha-helicity directly correlates with antibacterial activity against both Gram-positive and Gram-negative bacteria. Serum inhibits both antibacterial and cytotoxic activities. Circular dichroism (CD) spectroscopy, minimum inhibitory concentration (MIC) assay, cytotoxicity assay, serum inhibition experiment The Journal of biological chemistry High 9452503
1998 Apolipoprotein A-I (apoA-I) is the principal LL-37 binding protein in human plasma. ApoA-I was isolated by LL-37 affinity chromatography and binds LL-37 with an apparent Kd in the low micromolar range (surface plasmon resonance). ApoA-I at 50 µM inhibits ~50% of LL-37 antibacterial activity, and anti-apoA-I IgG blocks plasma inhibition of LL-37, indicating apoA-I acts as a scavenger of LL-37 in plasma. Affinity chromatography, SDS-PAGE, amino acid sequence analysis, surface plasmon resonance (Biacore), antimicrobial assay, blocking with anti-apoA-I antibody The Journal of biological chemistry High 9837875
1998 CAP18/LL-37 is expressed in developing neutrophils in human bone marrow in a lineage- and stage-specific manner: CAMP mRNA is transcribed predominantly at the myelocyte stage, while CAP18 protein accumulates and persists through metamyelocytes, band cells, and segmented neutrophils, indicating post-transcriptional regulation and cytoplasmic storage. Northern blot, Western blot, in situ hybridization, immunohistochemistry of bone marrow cells and mature neutrophils Journal of leukocyte biology High 9850169
2000 LL-37 is chemotactic for human peripheral blood monocytes, neutrophils, and T lymphocytes via formyl peptide receptor-like 1 (FPRL1). LL-37 induces Ca2+ mobilization in monocytes and FPRL1-transfected HEK293 cells, and this mobilization is cross-desensitized by an FPRL1-specific agonist, establishing FPRL1 as a functional receptor for LL-37-mediated leukocyte chemotaxis. Chemotaxis assay, Ca2+ mobilization assay in monocytes and FPRL1-transfected HEK293 cells, cross-desensitization experiment The Journal of experimental medicine High 11015447
2000 LL-37 is expressed by specific lymphocyte and monocyte populations including NK cells, γδ T cells, B cells, and monocytes/macrophages but not αβ T cells. Primary lymphocyte cultures transcribe and secrete LL-37, and this is modulated by IL-6 and IFN-γ. LL-37 has chemotactic activity for PMNs and CD4+ T lymphocytes. RT-PCR of cell lines, double-staining immunohistochemistry, primary lymphocyte culture, chemotaxis assay Blood High 11049988
2001 The human cathelicidin hCAP-18 is cleaved extracellularly by proteinase 3 (from azurophil granules) to generate the active antimicrobial peptide LL-37. Cleavage occurs after exocytosis, not during phagocytosis. Of the three serine proteases from azurophil granules (elastase, cathepsin G, proteinase 3), only proteinase 3 was responsible for this processing. Immunoelectron microscopy, immunoblotting of exocytosed material, selective protease inhibitors, identification of cleaving protease among the three azurophil serine proteases Blood High 11389039
2001 CAP18 (hCAP18/LL-37) and guinea pig CAP11 inhibit LPS-induced TNF-α expression in macrophages by blocking LPS binding to CD14+ cells. Mechanistically, CAP18 binds LPS with high affinity, competes with LPS-binding protein (LBP) for LPS transport to CD14, and also binds directly to cell surface CD14, thereby blocking LPS-CD14 interaction. Flow cytometry (FITC-LPS binding), Northern blot, Western blot for TNF-α, LPS-binding activity assay, LBP competition assay, in vivo mouse endotoxin shock model Journal of immunology High 11544322
2002 LL-37 is a multifunctional immunomodulator: at physiological concentrations it inhibits LPS, lipoteichoic acid, and noncapped lipoarabinomannan stimulation of macrophages; protects mice from lethal endotoxemia; directly up-regulates 29 macrophage genes including chemokines (MCP-1, IL-8) and chemokine receptors (CXCR-4, CCR2, IL-8RB) without inducing TNF-α; and reduces NF-κB nuclear translocation (p50 and p65 reduced >50%) in LPS-treated cells. Gene expression microarray, RT-PCR, ELISA, NF-κB nuclear translocation assay, in vivo mouse endotoxemia survival assay Journal of immunology High 12244186
2003 LL-37/hCAP-18 induces angiogenesis via formyl peptide receptor-like 1 (FPRL1) expressed on endothelial cells. LL-37 directly activates endothelial cell proliferation and tube formation in vitro, promotes neovascularization in the chorioallantoic membrane assay and a rabbit hind-limb ischemia model, and mice deficient for CRAMP (the murine ortholog) show decreased vascularization during wound repair in vivo. In vitro endothelial cell proliferation and tube formation assay, chorioallantoic membrane (CAM) angiogenesis assay, rabbit hind-limb ischemia model, CRAMP-knockout mouse wound healing model The Journal of clinical investigation High 12782669
2003 LL-37 is expressed in healing skin epithelium and is required for re-epithelialization. hCAP18 levels peak at 48 h post-wounding then decline; it is detected in inflammatory infiltrate and migrating epithelium. In an ex vivo organ culture wound model, anti-LL-37 antibodies inhibit re-epithelialization in a concentration-dependent manner and abolish Ki67 (proliferation marker) staining in wound-edge epithelium. LL-37 is markedly reduced in chronic non-healing ulcers. Immunohistochemistry, in situ hybridization, ex vivo wound healing organ culture model with blocking antibody, Ki67 proliferation assay The Journal of investigative dermatology High 12603850
2003 LL-37 disrupts lipid bilayers via a toroidal pore mechanism. Solid-state 15N NMR of site-specifically labeled LL-37 in oriented lipid bilayers shows the amphipathic helix lies parallel to the bilayer surface (ruling out barrel-stave mechanism). 31P NMR shows no micelle/small fragment formation (ruling out detergent-like mechanism), and LL-37 increases the lamellar-to-inverted hexagonal phase transition temperature of PE and E. coli lipids, indicating positive curvature strain consistent with toroidal pore formation. Solid-state 15N NMR (chemical shift and dipolar-shift spectroscopy of isotopically labeled peptide in oriented bilayers), 31P NMR, model membrane lipid phase transition analysis Biochemistry High 12767238
2004 LL-37 activates the P2X7 receptor to induce caspase-1 activation, IL-1β processing and release from LPS-primed monocytes. LL-37 induces transient ATP release, membrane permeability changes, and IL-1β secretion without cytotoxicity. Pretreatment with P2X7 inhibitors (oxidized ATP, KN04, KN62) suppresses IL-1β release. Apyrase (which hydrolyzes ATP) does not block LL-37's effect, indicating LL-37 directly activates P2X7 rather than acting via autocrine ATP. IL-1β ELISA, caspase-1 activity assay, membrane permeability assay, pharmacological P2X7 inhibitors, apyrase treatment Journal of immunology High 15067080
2004 The C-terminal domain of hCAP18 (hCAP18(109-135)) induces caspase-independent apoptosis selectively in oral squamous cell carcinoma (SAS-H1) cells but not in normal human gingival fibroblasts or HaCaT keratinocytes. The mechanism involves mitochondrial membrane depolarization without caspase activation. Cell viability assay, mitochondrial depolarization assay (JC-1), caspase activation assay, specificity comparison between cancer and normal cells Cancer letters Medium 15279899
2006 TLR2/1 activation of human macrophages upregulates expression of vitamin D receptor and vitamin D-1-hydroxylase, leading to induction of cathelicidin (CAMP gene product LL-37) and killing of intracellular Mycobacterium tuberculosis. Low serum 25-hydroxyvitamin D in African-American individuals correlates with failure to support cathelicidin mRNA induction, linking vitamin D status to TLR-mediated CAMP gene expression. TLR ligand stimulation of macrophages, RT-PCR for CAMP/VDR/CYP27B1, intracellular M. tuberculosis killing assay, serum 25-hydroxyvitamin D measurement and cathelicidin mRNA induction correlation Science High 16497887
2006 Vitamin D (1,25-dihydroxyvitamin D3) triggers antimicrobial activity against intracellular M. tuberculosis in human THP-1 monocytes via induction of cathelicidin. siRNA knockdown of cathelicidin mRNA and protein expression completely inhibits 1,25D3-induced antimicrobial activity and leads to enhanced intracellular mycobacterial growth, demonstrating that cathelicidin is required for (not merely associated with) this pathway. siRNA knockdown, RT-PCR, Western blot, intracellular M. tuberculosis growth assay in THP-1 cells Journal of immunology High 17675463
2006 Cathelicidin (LL-37/CRAMP) is essential for urinary tract innate immunity. Epithelial cells of human and mouse urinary tract produce LL-37/hCAP-18 and CRAMP respectively upon bacterial contact. CRAMP-deficient mice and neutrophil-depleted mice show significantly impaired protection against E. coli urinary tract infection. Clinical E. coli strains more resistant to LL-37 cause more severe UTIs, establishing a causal antimicrobial role. In situ hybridization, immunohistochemistry, Western blot of urine, CRAMP-knockout mouse infection model, neutrophil depletion, clinical E. coli strain susceptibility comparison Nature medicine High 16751768
2006 Kallikrein serine proteases (SCTE/kallikrein-5 and SCCE/kallikrein-7) in the stratum corneum control activation of hCAP18 to LL-37 and further processing to smaller cathelicidin peptides with distinct biological activities. SPINK5-deficient mice (lacking LEKTI serine protease inhibitor) show increased epidermal antimicrobial activity that is ablated by immunoabsorption of cathelicidin, demonstrating that the balance of protease activity at epithelial surfaces controls cathelicidin-mediated innate defense. Selective serine protease inhibitors, SELDI-TOF-MS, Western blot, siRNA for SCTE/SCCE, SPINK5-knockout mice, immunoabsorption of cathelicidin from epidermal extracts, antimicrobial assay FASEB journal High 17012259
2007 LL-37 is the key factor mediating plasmacytoid dendritic cell (pDC) activation in psoriasis. LL-37 binds self-DNA to form aggregated, condensed structures that are delivered to and retained in early endocytic compartments of pDCs, where they trigger TLR9 to induce type I IFN production. This defines LL-37 as a factor that breaks innate tolerance to self-DNA. pDC stimulation assays, IFN-α ELISA, confocal microscopy of LL-37-DNA complex uptake into endosomes, TLR9 reporter assays, gel retardation assay for LL-37-DNA complex structure Nature High 17873860
2007 Rosacea skin shows abnormally high cathelicidin (CAMP gene product) levels and unique proteolytically processed cathelicidin peptide forms, resulting from increased stratum corneum tryptic enzyme (SCTE) activity in the epidermis. Injection of rosacea-specific cathelicidin peptides or SCTE into mouse skin increases inflammation. Targeted deletion of Camp in mice confirms that cathelicidin is required for SCTE-mediated skin inflammation. Immunohistochemistry, ELISA, mass spectrometry peptide identification, intradermal injection of peptides in mice, SCTE transgenic mice, Spink5-knockout mice, Camp-knockout mice Nature medicine High 17676051
2007 LL-37 binding selectivity between bacterial and host cell membranes is determined by lipid composition: LL-37 intercalates into anionic phospholipid-containing membranes (bacterial membranes) but shows strongly attenuated intercalation into membranes containing both cholesterol and sphingomyelin (characteristic of host cell outer leaflets). LL-37 may form cytotoxic oligomers similarly to amyloid-like peptides in the presence of anionic phospholipids. Minimum inhibitory concentration assay, dynamic light scattering, lipid monolayer penetration, fluorescence spectroscopy with Trp-containing LL-37 mutant (F27W) Biochimica et biophysica acta Medium 18166145
2008 The three-dimensional NMR structure of LL-37 in SDS and dioctanoylphosphatidylglycerol (D8PG) micelles reveals a curved amphipathic helix-bend-helix motif (residues 2–31) with a bend between Gly-14 and Glu-16, followed by a disordered C-terminal tail. Intermolecular NOE cross-peaks between aromatic residues (Phe-5, -6, -17, -27) and arginines with D8PG provide direct evidence for helix association with anionic lipid micelles. The minimal antibacterial peptide KR-12 (residues 18–29) forms a short amphipathic helix with selective toxicity toward bacteria. 3D triple-resonance NMR spectroscopy of 13C,15N-labeled LL-37, intermolecular NOE measurements with D8PG micelles, synthetic peptide MIC assay, cytotoxicity assay The Journal of biological chemistry High 18818205
2008 LL-37 increases TLR4 mRNA and protein levels in mast cells and induces release of IL-4, IL-5, and IL-1β. When LL-37 co-exists with LPS (TLR4 ligand), Th2 cytokine upregulation is cancelled but pro-inflammatory cytokine augmentation is maintained, demonstrating a switch of mast cell function toward innate immunity. RT-PCR, Western blot, ELISA for cytokines in mast cell (RBL-2H3) cultures treated with LL-37 ± LPS Biological & pharmaceutical bulletin Medium 18239275
2009 LL-37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). Self-RNA–LL-37 complexes activate TLR7 in pDCs (inducing IFN-α) and TLR8 in mDCs (inducing TNF-α/IL-6 and DC maturation). Self-RNA–LL-37 complexes are present in psoriatic skin lesions associated with mature mDCs in vivo. pDC and mDC stimulation assays, IFN-α/TNF-α ELISA, TLR blocking antibodies, TLR7/TLR8 reporter assays, RNA protection assay, immunohistochemistry of psoriatic skin The Journal of experimental medicine High 19703986
2012 LL-37 transports extracellular self-DNA into monocytes via a TLR-independent pathway. Once inside monocytes, self-DNA activates cytosolic DNA sensors requiring the adaptor protein STING and TBK1 kinase to induce type I IFNs. This activation is mediated by double-stranded B-form DNA regardless of sequence, CpG content, or methylation status. Type I IFN induction assay, pharmacological inhibitors of endosomal TLRs, siRNA knockdown of STING and TBK1, confocal microscopy of DNA uptake, synthetic DNA with varying CpG content/methylation Blood High 22927244
2012 LL-37 and NETs activate the NLRP3 inflammasome in human and murine macrophages, causing caspase-1 activation and release of active IL-1β and IL-18. LL-37 activates NLRP3 via P2X7 receptor-mediated potassium efflux. This inflammasome activation is enhanced in lupus patient macrophages, and IL-18 in turn stimulates further NETosis, creating a feed-forward inflammatory loop. Caspase-1 activation assay, IL-1β/IL-18 ELISA, NLRP3 inflammasome inhibitors, P2X7 inhibitors, potassium efflux measurement, macrophages from lupus patients vs. controls, NETosis assay Journal of immunology High 23267025
2014 LL-37 is a T-cell autoantigen in psoriasis: CD4+ and/or CD8+ T cells specific for LL-37 are present in two-thirds of patients with moderate-to-severe plaque psoriasis, produce IFN-γ and Th17 cytokines, infiltrate lesional skin (tracked by MHC tetramer staining), and their prevalence correlates with disease activity. MHC-peptide tetramer staining, intracellular cytokine staining, flow cytometry, immunohistochemistry of lesional skin biopsies, correlation analysis with PASI score Nature communications High 25470744
2015 Commensal anaerobic bacteria (clostridial Firmicutes and Bacteroidetes) maintain C. albicans colonization resistance in mice by activating HIF-1α, which induces expression of the cathelicidin CRAMP (murine CAMP ortholog). Pharmacological HIF-1α activation induces CRAMP and reduces C. albicans colonization and mortality. In the presence of antibiotics, Hif1a and Camp (CRAMP) are required for Bacteroides thetaiotaomicron-induced protection. Antibiotic-treated and germ-free mouse models, pharmacological HIF-1α activators, Camp-knockout and Hif1a-knockout mice, C. albicans colonization quantification, survival analysis Nature medicine High 26053625
2016 LL-37 and double-stranded RNA released from necrotic cells activate MAVS (mitochondrial antiviral-signaling protein) in keratinocytes, triggering a TBK1→AKT→IRF3 signaling cascade that leads to IFN-β production and dendritic cell maturation. MAVS-deficient mice show impaired epidermal IFN-β production by LL-37, and psoriatic/wounded human skin shows MAVS-associated IRF3 activation and IFN-β gene signatures. MAVS-knockout mice, siRNA knockdown of MAVS in keratinocytes, IFN-β ELISA, IRF3 phosphorylation assay, Western blot for TBK1/AKT/IRF3, immunohistochemistry of human psoriatic skin Immunity High 27438769
2016 Histone deacetylase inhibitor Entinostat up-regulates CAMP gene expression via a STAT3→HIF-1α transcriptional axis. Entinostat activates STAT3, which promotes HIF-1α expression; only HIF-1α (not STAT3) is directly recruited to the CAMP promoter. This was confirmed using shRNA knockdown and selective inhibitors, and in macrophages from a STAT3-mutant patient where Entinostat-elicited LL-37 expression was impaired. Luciferase reporter assay (CAMP promoter), shRNA knockdown of STAT3 and HIF-1α, selective inhibitors, ChIP assay showing HIF-1α recruitment to CAMP promoter, macrophages from STAT3-mutant patient Scientific reports High 27633343
2018 LL-37 activates platelets and enhances thrombus formation via formyl peptide receptor 2 (FPR2/ALX). LL-37 activates a range of platelet functions and shortens tail bleeding time in mice. Using a pharmacological FPR2/ALX inhibitor and Fpr2/3-deficient mice, platelet activation, thrombus formation, and hemostatic effects of LL-37 were abolished, establishing FPR2/ALX as the functional receptor. Platelet aggregation assay, thrombus formation assay (flow chamber), tail bleeding time in mice, pharmacological FPR2/ALX inhibitor, Fpr2/3-knockout mice Blood advances High 30413433
2018 MrgX2 (a G protein-coupled receptor) mediates LL-37 internalization and mast cell degranulation. LL-37 is rapidly internalized into LAD2 mast cells via clathrin-mediated endocytosis dependent on negatively charged sialic acid at the cell surface. siRNA knockdown of MrgX2 inhibits both LL-37 internalization and degranulation; MrgX2 overexpression enhances LL-37 internalization. Pertussis toxin (G-protein inhibitor) suppresses both processes. Internalized LL-37 co-localizes with MrgX2 in the perinuclear region. siRNA knockdown of MrgX2, stable MrgX2 overexpression in HMC-1 and HEK293 cells, clathrin endocytosis inhibitors (dynasore, chlorpromazine), pertussis toxin, neuraminidase treatment, β-hexosaminidase degranulation assay, confocal microscopy Molecular medicine reports High 30280189
2020 Neutrophil extracellular trap (NET)-associated RNA (naRNA) in complex with LL-37 triggers a self-propagating inflammatory cycle in psoriasis. RNA (not canonical NET DNA) complexed with LL-37 activates TLR8/TLR13-mediated cytokine and NET release by primary murine and human neutrophils in vitro and in vivo. Transfer of NETs to naive human neutrophils prompts additional NET release. Primary murine and human PMN stimulation assays, TLR8 and TLR13 blocking/knockout, cytokine ELISA, NET quantification (MPO-DNA ELISA), in vivo neutrophil activation model, RNA vs. DNA complex comparison in psoriatic vs. normal skin Nature communications High 31913271
2021 LL-37 and HMGB1 induce RAGE-dependent alveolar epithelial damage and impair lung tissue repair. Intranasal LL-37 and HMGB1 cause RAGE-dependent inflammation and alveolar tissue damage in mice within 6 h; RAGE-deficient mice are protected. RAGE inhibition reduces recovery from elastase-induced alveolar damage in precision-cut lung slices. In organoids, RAGE ligands reduce organoid-forming efficiency. siRNA knockdown of RAGE in A549 cells confirms RAGE's role in LL-37-induced impaired repair. RAGE-knockout mice, RAGE inhibitor (FPS-ZM1), siRNA knockdown in A549 cells, precision-cut lung slices (PCLS), lung organoids, intranasal instillation model, histology American journal of physiology. Lung cellular and molecular physiology High 34405719
2022 LL-37 functions as a transporter of cyclic 2',3'-GMP-AMP (cGAMP) into target cells. LL-37 specifically binds cGAMP and delivers it intracellularly, activating robust STING-dependent interferon responses and host antiviral immunity. Vitamin D3 and sodium butyrate promote endogenous LL-37 expression and thereby enhance cGAMP-mediated immune responses. This identifies LL-37 as a cGAMP carrier bridging extracellular STING pathway activation. cGAMP-LL-37 binding assay, cell-based cGAMP delivery assay, IFN reporter assay, STING-knockout cells, antiviral immunity assay in vivo, LL-37 induction by vitamin D3/butyrate Cell reports High 35649354
1993 The C-terminal 37-amino acid domain of rabbit CAP18 (CAP18(106-142)) is the LPS-binding and antimicrobial domain, with broad bactericidal activity against Gram-positive and Gram-negative bacteria including S. aureus, S. pneumoniae, E. coli, P. aeruginosa, and S. typhimurium. Antimicrobial activity is highly dependent on peptide structure (helix integrity), and a 32-residue truncation from the C-terminus retains high activity while N-terminal truncation abolishes it. Unusually, CAP18(106-142) retains activity in serum. Synthetic peptide MIC assay against multiple bacterial strains, truncation variant activity comparison, serum stability assay Antimicrobial agents and chemotherapy High 8109914
1994 The primary antibacterial domain of rabbit CAP18 is a 21-residue cationic amphipathic alpha-helical sequence. Synthetic peptide has potent bactericidal activity against Gram-positive and Gram-negative bacteria and rapidly permeabilizes the E. coli inner membrane. Helix disruption (analogue synthesis) virtually eliminates antibacterial activity, while amphipathicity and the presence of an aromatic residue affect the kinetics of inner membrane permeabilization. Secondary structure prediction, synthetic peptide MIC assay, E. coli inner membrane permeabilization assay, synthesis of five analogues with helix-disrupting or amphipathicity-modifying substitutions FEBS letters High 8313956
1999 Rabbit CAP18 interacts with the outer membrane of Gram-negative bacteria by adsorbing to lipopolysaccharide-containing leaflets and forming transient membrane lesions (ion-conducting pores). Electron microscopy shows outer membrane damage in sensitive E. coli but not resistant P. mirabilis R45. Voltage-clamp experiments on asymmetric planar bilayers show that CAP18 adsorbs to LPS-containing leaflets and forms transient current fluctuations (membrane lesions) at a lipid-specific clamp voltage, indicating voltage-dependent reorientation into a transmembrane configuration. Transmission electron microscopy of bacteria, voltage-clamp electrophysiology on planar asymmetric bilayer membranes with LPS or phospholipid leaflets Biochemistry High 10521271
2000 Rabbit CAP18 intercalates into LPS-containing lipid matrices from sensitive bacterial strains but only weakly into LPS from resistant P. mirabilis R45 or negatively charged phospholipids, and not at all into neutral phosphatidylcholine. The L-Arap4N modification linked to the first Kdo residue of P. mirabilis R45 LPS is responsible for CAP18 resistance. The depth of intercalation is determined by structural differences in LPS, as shown by combined FRET, FTIR spectroscopy, and film balance measurements. Fluorescence resonance energy transfer (FRET), Fourier-transform infrared spectroscopy (FTIR), film balance (Langmuir trough) measurements on LPS/phospholipid monolayers and liposomes The Journal of membrane biology High 10931974

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science (New York, N.Y.) 2801 16497887
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2007 Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 1414 17873860
2000 LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. The Journal of experimental medicine 923 11015447
2010 The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PloS one 846 20209079
2003 An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. The Journal of clinical investigation 706 12782669
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2001 Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 672 11389039
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2007 Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature medicine 638 17676051
1997 The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders. The Journal of biological chemistry 617 9182550
2007 Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. Journal of immunology (Baltimore, Md. : 1950) 615 17675463
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2000 The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 602 11049988
2009 Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. The Journal of experimental medicine 578 19703986
1998 The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proceedings of the National Academy of Sciences of the United States of America 569 9689116
2002 The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. Journal of immunology (Baltimore, Md. : 1950) 557 12244186
1998 Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37. The Journal of biological chemistry 521 9452503
2006 The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nature medicine 492 16751768
1996 The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. European journal of biochemistry 450 8681941
2006 Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. Journal of immunology (Baltimore, Md. : 1950) 444 16456005
1995 Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infection and immunity 444 7890387
2012 A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cellular immunology 440 23246832
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2006 Epac proteins: multi-purpose cAMP targets. Trends in biochemical sciences 436 17084085
2003 The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. The Journal of investigative dermatology 435 12603850
2014 The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nature communications 419 25470744
2012 Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages. Journal of immunology (Baltimore, Md. : 1950) 418 23267025
2003 Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37. Biochemistry 410 12767238
1995 FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proceedings of the National Academy of Sciences of the United States of America 401 7529412
2004 Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proceedings of the National Academy of Sciences of the United States of America 400 15545605
2000 cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nature cell biology 387 11056535
2008 Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. The Journal of biological chemistry 375 18818205
2006 Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 355 17012259
2004 A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. Journal of immunology (Baltimore, Md. : 1950) 350 15067080
2009 Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends in biochemical sciences 348 19864144
2015 Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nature medicine 339 26053625
1995 Transcription factors responsive to cAMP. Annual review of cell and developmental biology 315 8689562
2009 The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Current opinion in hematology 222 19068548
2020 Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis. Nature communications 211 31913271
2001 Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. Journal of immunology (Baltimore, Md. : 1950) 206 11544322
2011 Wound healing activity of the human antimicrobial peptide LL37. Peptides 199 21693141
2003 Staphylococcus aureus susceptibility to innate antimicrobial peptides, beta-defensins and CAP18, expressed by human keratinocytes. Infection and immunity 184 12819054
2014 Endosomal generation of cAMP in GPCR signaling. Nature chemical biology 180 25271346
2011 FRET measurements of intracellular cAMP concentrations and cAMP analog permeability in intact cells. Nature protocols 177 21412271
2014 PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing. Journal of controlled release : official journal of the Controlled Release Society 176 25173841
1984 Competitive cAMP antagonists for cAMP-receptor proteins. The Journal of biological chemistry 150 6088478
2016 Antimicrobial Peptide LL37 and MAVS Signaling Drive Interferon-β Production by Epidermal Keratinocytes during Skin Injury. Immunity 148 27438769
2012 Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 145 22927244
1989 The mRNA encoding a high-affinity cAMP phosphodiesterase is regulated by hormones and cAMP. Proceedings of the National Academy of Sciences of the United States of America 144 2554303
2013 cAMP and mitochondria. Physiology (Bethesda, Md.) 134 23636265
1998 Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37. The Journal of biological chemistry 121 9837875
1991 Complementary DNA sequence of rabbit CAP18--a unique lipopolysaccharide binding protein. Biochemical and biophysical research communications 119 1883348
1984 Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases. European journal of biochemistry 115 6086345
2020 Significance of LL-37 on Immunomodulation and Disease Outcome. BioMed research international 111 32509872
2004 C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells. Cancer letters 110 15279899
2007 Binding of LL-37 to model biomembranes: insight into target vs host cell recognition. Biochimica et biophysica acta 106 18166145
2003 Mechanism of action of ACTH: beyond cAMP. Microscopy research and technique 102 12768543
2021 Vertebrate cells differentially interpret ciliary and extraciliary cAMP. Cell 96 33932338
1987 Phosphorylation of purified insulin receptor by cAMP kinase. Diabetes 96 3539674
2016 Mitochondrial cAMP signaling. Cellular and molecular life sciences : CMLS 94 27233501
2016 Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. Proceedings of the National Academy of Sciences of the United States of America 94 27357676
2014 Cyclic AMP (cAMP) signaling in melanocytes and melanoma. Archives of biochemistry and biophysics 94 25017568
2005 Expression and activity of beta-defensins and LL-37 in the developing human lung. Journal of immunology (Baltimore, Md. : 1950) 94 15661923
1998 Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia. Infection and immunity 94 9573062
2015 Unique features of human cathelicidin LL-37. BioFactors (Oxford, England) 91 26434733
1994 Identification and characterization of a primary antibacterial domain in CAP18, a lipopolysaccharide binding protein from rabbit leukocytes. FEBS letters 91 8313956
2018 Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37. International journal of antimicrobial agents 90 29753132
2005 Compartmentalization of adenylate cyclase and cAMP signalling. Biochemical Society transactions 86 16246108
1991 Transcriptional regulation by cAMP. Current opinion in cell biology 82 1667580
1993 Antimicrobial activity of rabbit CAP18-derived peptides. Antimicrobial agents and chemotherapy 81 8109914
2009 Extracellular 2',3'-cAMP is a source of adenosine. The Journal of biological chemistry 79 19801686
2022 LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity. Cell reports 76 35649354
2002 cAMP signaling in Dictyostelium. Complexity of cAMP synthesis, degradation and detection. Journal of muscle research and cell motility 76 12952077
2018 PDE4-Mediated cAMP Signalling. Journal of cardiovascular development and disease 75 29385021
1994 Characterization of a rabbit cationic protein (CAP18) with lipopolysaccharide-inhibitory activity. Infection and immunity 75 8132348
2016 Mechanisms Restricting Diffusion of Intracellular cAMP. Scientific reports 73 26795432
2009 LL-37 promotes rapid sensing of CpG oligodeoxynucleotides by B lymphocytes and plasmacytoid dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 70 20042575
2013 CFTR: a hub for kinases and crosstalk of cAMP and Ca2+. The FEBS journal 69 23895508
2000 What is a cAMP response unit? Molecular and cellular endocrinology 66 10854692
2005 Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats. Pediatric surgery international 64 15645239
1995 Anti-microbial activity of human CAP18 peptides. Immunotechnology : an international journal of immunological engineering 61 9373334
1995 The solution structure of the active domain of CAP18--a lipopolysaccharide binding protein from rabbit leukocytes. FEBS letters 60 7649303
2020 Topical nanoparticles interfering with the DNA-LL37 complex to alleviate psoriatic inflammation in mice and monkeys. Science advances 59 32923608
2011 Antimicrobial and antibiofilm activity of LL-37 and its truncated variants against Burkholderia pseudomallei. International journal of antimicrobial agents 59 22005071
2018 Interaction of 2',3'-cAMP with Rbp47b Plays a Role in Stress Granule Formation. Plant physiology 58 29618637
2014 cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP). Biochemical Society transactions 57 24450633
1996 Structural, functional analysis and localization of the human CAP18 gene. FEBS letters 57 8946956
2008 Human cathelicidin CAP18/LL-37 changes mast cell function toward innate immunity. Biological & pharmaceutical bulletin 56 18239275
2002 Extracellular cAMP inhibits proximal reabsorption: are plasma membrane cAMP receptors involved? American journal of physiology. Renal physiology 54 11832418
2012 [Regulation of melanogenesis: the role of cAMP and MITF]. Postepy higieny i medycyny doswiadczalnej (Online) 53 22371403
1998 Evaluation of antimicrobial and lipopolysaccharide-neutralizing effects of a synthetic CAP18 fragment against Pseudomonas aeruginosa in a mouse model. Antimicrobial agents and chemotherapy 53 9835525
2012 Role of defensins and cathelicidin LL37 in auto-immune and auto-inflammatory diseases. Current pharmaceutical biotechnology 51 22250708
2024 LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules 49 38540740
2022 Delivery LL37 by chitosan nanoparticles for enhanced antibacterial and antibiofilm efficacy. Carbohydrate polymers 47 35698353
2019 LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation. Frontiers in immunology 46 30842778
2018 The endogenous antimicrobial cathelicidin LL37 induces platelet activation and augments thrombus formation. Blood advances 46 30413433
2016 Entinostat up-regulates the CAMP gene encoding LL-37 via activation of STAT3 and HIF-1α transcription factors. Scientific reports 41 27633343
2015 Antimicrobial peptide FF/CAP18 induces apoptotic cell death in HCT116 colon cancer cells via changes in the metabolic profile. International journal of oncology 41 25672949
1995 Dual role of cAMP during Dictyostelium development. Experientia 41 8536804
2012 Interactions between calcium and cAMP signaling. Current medicinal chemistry 40 22963560
2000 Transcriptional regulation by cAMP in the heart. Molecular and cellular biochemistry 40 11108131
2014 Serum levels of LL-37 and inflammatory cytokines in plaque and guttate psoriasis. Mediators of inflammation 38 25197165
1990 Characteristics of the cAMP response unit. Metabolism: clinical and experimental 38 2169573
2022 The adipocyte supersystem of insulin and cAMP signaling. Trends in cell biology 37 35989245
2024 cAMP signaling: a remarkably regional affair. Trends in biochemical sciences 36 38310024
2012 Multiple facets of cAMP signalling and physiological impact: cAMP compartmentalization in the lung. Pharmaceuticals (Basel, Switzerland) 36 24281338
2004 Involvement of cAMP in neuronal survival and axonal regeneration. Anatomical science international 36 15633459
2010 Regulation of cAMP by phosphodiesterases in erythrocytes. Pharmacological reports : PR 35 20631411
1998 Evaluation of the expression of human CAP18 gene during neutrophil maturation in the bone marrow. Journal of leukocyte biology 35 9850169
2020 Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis. Pigment cell & melanoma research 34 32777162
1996 Single cell Ca2+/cAMP cross-talk monitored by simultaneous Ca2+/cAMP fluorescence ratio imaging. Proceedings of the National Academy of Sciences of the United States of America 34 8643446
2008 Role of cAMP in mediating AHR signaling. Biochemical pharmacology 33 19013136
2017 Discovery and Roles of 2',3'-cAMP in Biological Systems. Handbook of experimental pharmacology 32 26721674
2022 LL-37, a Multi-Faceted Amphipathic Peptide Involved in NETosis. Cells 30 35954305
2022 2',3'-cAMP treatment mimics the stress molecular response in Arabidopsis thaliana. Plant physiology 29 35043968
2018 LL-37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis-induced acute lung injury. Journal of cellular biochemistry 29 30537236
2011 cAMP during HIV infection: friend or foe? AIDS research and human retroviruses 29 21916808
2002 cAMP pathway in podocytes. Microscopy research and technique 29 12012389
2015 A dynamic interface between ubiquitylation and cAMP signaling. Frontiers in pharmacology 28 26388770
2006 Anchored cAMP signaling: onward and upward - a short history of compartmentalized cAMP signal transduction. European journal of cell biology 27 16524641
2021 NETs Lead to Sympathetic Hyperactivity After Traumatic Brain Injury Through the LL37-Hippo/MST1 Pathway. Frontiers in neuroscience 26 33994918
2003 Sensitivity of genera Porphyromonas and Prevotella to the bactericidal action of C-terminal domain of human CAP18 and its analogues. Oral microbiology and immunology 26 12930528
2000 Mechanisms of action of rabbit CAP18 on monolayers and liposomes made from endotoxins or phospholipids. The Journal of membrane biology 26 10931974
1999 Molecular mechanisms of interaction of rabbit CAP18 with outer membranes of gram-negative bacteria. Biochemistry 26 10521271
1995 Protective effects of a novel 32-amino acid C-terminal fragment of CAP18 in endotoxemic pigs. Surgery 26 7778029
2021 LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE. American journal of physiology. Lung cellular and molecular physiology 25 34405719
2018 MrgX2‑mediated internalization of LL‑37 and degranulation of human LAD2 mast cells. Molecular medicine reports 25 30280189
1999 Dictyostelium development-socializing through cAMP. Seminars in cell & developmental biology 25 10706821
2021 Macropinocytosis-Inducible Extracellular Vesicles Modified with Antimicrobial Protein CAP18-Derived Cell-Penetrating Peptides for Efficient Intracellular Delivery. Molecular pharmaceutics 23 34365796