Affinage

SLPI

Antileukoproteinase · UniProt P03973

Length
132 aa
Mass
14.3 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLPI is a small (~12 kDa), 107-residue secreted serine protease inhibitor built from two tandem WAP four-disulfide-core domains that broadly inhibits neutrophil elastase, cathepsin G, chymotrypsin, trypsin, mast cell chymase, and tryptase, with the protease-inhibitory active site residing in its C-terminal domain (PMID:3485543, PMID:3060147, PMID:8097952). Beyond direct antiprotease function, SLPI is a pleiotropic anti-inflammatory factor: it dampens macrophage and B cell inflammatory responses by attenuating NF-κB signaling, and this immunomodulatory activity is genetically separable from protease inhibition, since active-site mutants and isolated domains that lack antiprotease activity still suppress LPS responses (PMID:12615907, PMID:16112212). SLPI restrains adaptive and innate inflammation through several routes—inhibiting AID induction and immunoglobulin class switching in B cells (PMID:17259987), blocking ATP-driven inflammasome and caspase-1-dependent IL-1β release via an iPLA2β–nicotinic acetylcholine receptor–Src cascade (PMID:31019507), and limiting neutrophil extracellular trap formation by co-localizing with neutrophil elastase in the nucleus and inhibiting histone H4 cleavage (PMID:25917460). It is synthesized in myelocytes and stored in neutrophil secondary granules alongside lactoferrin for rapid release upon activation, and once secreted it can be covalently cross-linked to fibronectin and elastin by transglutaminases while retaining antiprotease activity (PMID:18285402, PMID:21687692). SLPI transcription is induced by IL-1β, TNF-α, TLR2 signaling (MyD88-independent), STAT1, TSLP, and Nrf2, and is repressed by IRF-1 and Mecp2, while its function is abolished by oxidative inactivation from cigarette smoke (PMID:7946401, PMID:16236128, PMID:24285265, PMID:21820333, PMID:23195333, PMID:10498899, PMID:31597640, PMID:11435216). In disease contexts SLPI acts as a context-dependent regulator of epithelial repair, hematopoietic differentiation, and tumor behavior, including a protease-inhibition-independent induction of MMP-9 and promotion of tumor invasion (PMID:21820333, PMID:24352879, PMID:21676452).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1986 High

    Established the molecular identity and architecture of SLPI, defining it as a two-WAP-domain disulfide-rich protein and unifying inhibitory activities isolated from multiple secretions as products of a single gene.

    Evidence Direct protein and cDNA sequencing from cervical tissue, plus in vitro inhibition assays against chymase and other proteases

    PMID:3060147 PMID:3485543 PMID:3530282

    Open questions at the time
    • Did not resolve which domain carries inhibitory activity
    • No structural mechanism of inhibition
  2. 1993 High

    Localized the protease-inhibitory function to the C-terminal WAP domain, showing the isolated domain inhibits neutrophil elastase and cathepsin G.

    Evidence In vitro enzymatic inhibition and platelet activation assays with recombinant full-length and truncated SLPI

    PMID:8097952

    Open questions at the time
    • Function of the N-terminal domain left undefined
    • Less potent than full-length, mechanism of cooperativity unclear
  3. 1998 High

    Mapped the SLPI gene structure and chromosomal location and identified the first transcriptional repressor (IRF-1), beginning the dissection of SLPI regulation.

    Evidence Genomic sequencing, FISH, RNA fingerprinting, EMSA, and promoter reporter assays

    PMID:10498899 PMID:9843921

    Open questions at the time
    • Repression mechanism and physiological context of IRF-1 control not established
  4. 2001 Medium

    Demonstrated that SLPI antiprotease function is lost by oxidation, providing a mechanism for its inactivation in cigarette smoke exposure.

    Evidence In vivo mouse intratracheal recombinant SLPI with cigarette smoke and N-acetylcysteine rescue, BAL antitryptic activity

    PMID:11435216

    Open questions at the time
    • Specific oxidized residues not identified in vivo
    • Single lab
  5. 2003 High

    Genetic knockout established SLPI as an endogenous restraint on NF-κB-mediated inflammation in macrophages and B cells in vivo.

    Evidence SLPI-/- mice, LPS challenge, macrophage cytokine and NF-κB reporter assays, B cell proliferation

    PMID:12615907

    Open questions at the time
    • Molecular target by which SLPI inhibits NF-κB not defined
    • Did not separate protease-dependent from independent effects
  6. 2005 High

    Proved that SLPI's anti-inflammatory activity is independent of its antiprotease activity using active-site mutants and isolated domains.

    Evidence Site-directed mutagenesis (M73 variants) and domain truncations in stable RAW264.7 macrophages with LPS readouts

    PMID:16112212

    Open questions at the time
    • Receptor/binding partner mediating immunomodulation not identified
  7. 2005 High

    Defined a TLR2-dependent, MyD88-independent induction pathway for SLPI, linking pathogen sensing to its expression.

    Evidence Macrophages from TLR2-/-, TLR4-/-, and MyD88-/- mice with M. tuberculosis stimulation

    PMID:16236128

    Open questions at the time
    • MyD88-independent transcriptional effectors downstream of TLR2 not mapped
  8. 2007 High

    Showed SLPI acts as a homeostatic brake on adaptive immunity by inhibiting AID induction and immunoglobulin class switching in B cells.

    Evidence Human tonsillar explant and B cell-epithelial co-culture with AID and class-switch readouts and SLPI blocking

    PMID:17259987

    Open questions at the time
    • Direct molecular link between SLPI and AID suppression unresolved
  9. 2008 High

    Identified SLPI as a neutrophil secondary granule protein co-stored and co-released with lactoferrin, defining its cellular reservoir in innate immunity.

    Evidence Microarray of bone marrow populations, subcellular fractionation, immunostaining, exocytosis assay

    PMID:18285402

    Open questions at the time
    • Trafficking and sorting determinants to secondary granules not defined
  10. 2011 High

    Showed secreted SLPI is covalently cross-linked into the extracellular matrix by transglutaminases while retaining inhibitory activity, explaining its matrix association.

    Evidence In vitro transglutaminase cross-linking to fibronectin/elastin, mass spectrometry site mapping, activity assays

    PMID:21687692

    Open questions at the time
    • Physiological significance of matrix-bound SLPI not tested in vivo
  11. 2011 High

    Established that SLPI can promote tumor invasion through protease-inhibition-independent MMP-9 induction, revealing a context-dependent pro-tumorigenic role.

    Evidence Protease-inhibitor-null SLPI mutant in ovarian cancer cells, invasion, MMP-9, xenograft, and tissue microarray

    PMID:21676452

    Open questions at the time
    • Transcriptional pathway from SLPI to MMP-9 not defined
    • Receptor mediating the effect unknown
  12. 2011 High

    Identified TSLP-induced epithelial SLPI as required for mucosal healing, linking SLPI induction to control of neutrophil elastase damage in colitis.

    Evidence Tslp-/- mice, DSS colitis, bone marrow chimeras, NE inhibitor and rSLPI rescue

    PMID:21820333

    Open questions at the time
    • Whether protection is purely via NE inhibition versus immunomodulation not fully separated
  13. 2013 High

    Showed SLPI controls myeloid progenitor proliferation, differentiation, and survival through NF-κB and ERK/LEF-1 signaling, and revealed reciprocal NE-SLPI regulation.

    Evidence shRNA knockdown in CD34+ progenitors, wild-type/mutant NE transduction, flow cytometry and pathway Western blots

    PMID:24352879

    Open questions at the time
    • Direct molecular link between SLPI and ERK/LEF-1 activation unclear
  14. 2013 High

    Defined STAT1 as a direct transcriptional activator of SLPI binding its promoter, integrating SLPI expression into interferon-responsive epithelial signaling.

    Evidence ChIP, promoter reporter assays, Stat1-/- mice, expression analysis in smokers

    PMID:24285265

    Open questions at the time
    • Interplay between STAT1 activation and IFN-γ-mediated suppression not reconciled
  15. 2015 High

    Demonstrated SLPI restrains NET formation by inhibiting nuclear histone H4 cleavage in co-localization with neutrophil elastase, defining a nuclear function in innate immunity.

    Evidence Human neutrophil NET assays, SLPI-/- neutrophils, H4 cleavage assay, nuclear immunofluorescence, psoriasis model

    PMID:25917460

    Open questions at the time
    • Mechanism of SLPI nuclear entry not established
  16. 2019 Medium

    Resolved the signaling pathway by which SLPI blocks inflammasome activation, implicating iPLA2β, nicotinic acetylcholine receptors, and Src kinase upstream of caspase-1.

    Evidence Human monocytic cells with siRNA/inhibitors for iPLA2β, nAChR subunits, caspase-1 assays, Xenopus oocyte electrophysiology

    PMID:31019507

    Open questions at the time
    • Identity of the low-molecular-mass mediator released by SLPI not defined
    • Direct SLPI receptor not identified
  17. 2019 High

    Identified Mecp2 as a direct promoter-binding repressor of SLPI controlling adipose browning, extending SLPI regulation to metabolic tissue.

    Evidence ChIP, fat-specific Mecp2 knockout, in vivo Slpi knockdown rescue, recombinant SLPI treatment

    PMID:31597640

    Open questions at the time
    • Downstream effector of SLPI in browning not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The cell-surface receptor(s) mediating SLPI's protease-independent immunomodulatory and signaling effects remain unidentified, leaving the mechanistic link between SLPI binding and intracellular NF-κB/ERK/MAPK outcomes unresolved.
  • No defined SLPI receptor across immune, hematopoietic, or tumor contexts
  • How SLPI accesses intracellular/nuclear compartments is unknown
  • Whether matrix-bound vs free SLPI signal differently is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2 GO:0005634 nucleus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ANXA2ELANEFOXM1RB1TUBB1

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 SLPI (antileukoprotease/HUSI-I) is a 107 amino acid, ~12 kDa protein containing 16 cysteines forming disulfide bonds, organized into two consecutive domains each with a 'four-disulfide-core' (WAP domain) structural motif homologous to chelonianin and whey proteins. The complete sequence was determined by both direct protein sequencing and cDNA sequencing from cervical tissue mRNA. Direct protein sequencing and cDNA cloning/sequencing FEBS letters High 3485543
1986 SLPI inhibits mast cell chymase; equimolar concentrations (~10 nM) of chymase and SLPI result in rapid complex formation, with 50% inhibition of chymase activity requiring ~700 nM SLPI (dissociation constant ~44 nM for the eglin c-chymase complex for comparison). SLPI thus functions as a direct inhibitor of mast cell chymase. In vitro enzymatic inhibition assay with purified proteins Biological chemistry Hoppe-Seyler High 3530282
1988 SLPI inhibits trypsin, chymotrypsin, granulocytic elastase, cathepsin G, mast cell chymase, and tryptase. The various forms isolated from different secretions (bronchial mucus, seminal plasma, cervical mucus, parotid secretion) are identical or derived from a single gene product. Biochemical characterization and enzymatic inhibition assays Biological chemistry Hoppe-Seyler High 3060147
1990 After intravenous injection, SLPI is rapidly cleared from plasma with an initial half-life of ~10 minutes, followed by slower clearance (~60-120 min). Radioactivity accumulated predominantly in kidneys, and renal metabolism of SLPI was demonstrated. Intact SLPI was not detected in urine, indicating renal catabolism rather than filtration. Radiolabeled (35S and 125I) SLPI pharmacokinetics in dogs and human volunteers, organ biodistribution Scandinavian journal of clinical and laboratory investigation Medium 2293334
1993 The C-terminal domain of SLPI (half-SLPI, Asn55-Ala107) alone is sufficient to inhibit neutrophil elastase and cathepsin G, and to inhibit cathepsin G-mediated platelet activation and PMN-mediated platelet activation, though less potently than full-length SLPI. This establishes the catalytic/inhibitory site resides in the C-terminal domain. In vitro enzymatic inhibition assay and platelet activation assay using recombinant full-length and truncated SLPI British journal of pharmacology High 8097952
1994 IL-1β and TNF-α induce significant SLPI expression in human airway epithelial cell lines (A549 and NCI-H322), identifying these cytokines as major transcriptional inducers of SLPI in the lung epithelium. Cell culture stimulation with cytokines, protein measurement in supernatants American journal of respiratory cell and molecular biology Medium 7946401
1997 SLPI purified from saliva or produced as recombinant protein inhibits HIV-1 infection of human monocytes in vitro at 100 ng/mL. Salivary levels of SLPI exceed this threshold, consistent with in vivo antiviral activity. Breast milk SLPI levels were insufficient to provide antiviral protection except in colostrum. In vitro HIV-1 infection assay with purified native and recombinant SLPI, ELISA quantification, Northern blot and immunohistochemistry Oral diseases Medium 9456660
1998 SLPI is inducibly expressed in migrating keratinocytes of healing wounds and in lesional psoriatic epidermis, but not in proliferating keratinocytes. Extracellular SLPI was found associated with elastin fibers in the dermis adjacent to SLPI-expressing keratinocytes. Recombinant SLPI exhibited antibacterial activity with a distinct spectrum compared to lysozyme and defensins. Immunohistochemistry, in situ hybridization, cell culture differentiation assays, antibacterial functional assays The Journal of investigative dermatology Medium 9856807
1998 SLPI gene is organized into four exons and three introns spanning ~2.2 kb with a transcription start site located 20 nt upstream of the ATG initiation codon. The human SLPI gene maps to chromosome 20q12-13.2 and the mouse homologue to chromosome 2H by fluorescence in situ hybridization. Genomic DNA sequencing, primer extension analysis, FISH American journal of respiratory cell and molecular biology High 9843921
1999 IRF-1 transcriptionally represses SLPI expression. RNA fingerprinting identified SLPI as downregulated upon IRF-1 induction; an ISRE-like binding site was mapped to the -221 to -200 region of the SLPI promoter to which IRF-1 binds, and co-transfection studies demonstrated that IRF-1 co-expression inhibits SLPI promoter activity. RNA fingerprinting, promoter deletion analysis, electrophoretic mobility shift assay (EMSA), co-transfection/reporter assays Oncogene Medium 10498899
2000 Neutrophil elastase (NE) increases SLPI mRNA levels in primary bronchial epithelial cells while simultaneously decreasing SLPI protein in supernatants by promoting accumulation of cell-associated SLPI. This apparent paradox is explained by NE causing SLPI retention at the cell surface rather than inhibiting SLPI synthesis. Primary bronchial epithelial cell culture, Northern blot, ELISA of supernatants and cell lysates Journal of investigative medicine Medium 10979241
2000 Neutrophil-derived alpha-defensins increase SLPI protein release from primary bronchial epithelial cells in a time- and dose-dependent manner without affecting SLPI mRNA levels, indicating post-transcriptional or post-translational regulation. Alpha-1-proteinase inhibitor further enhanced defensin-induced SLPI release. Primary bronchial epithelial cell culture, ELISA, Northern blot American journal of physiology. Lung cellular and molecular physiology Medium 10645890
2001 Cigarette smoke oxidatively inactivates human SLPI in vivo. In a mouse model, intratracheal human recombinant SLPI's antitryptic inhibitory activity was reduced by 50% following cigarette smoke exposure; this inactivation was prevented by N-acetylcysteine pretreatment, demonstrating oxidation-dependent loss of SLPI function. In vivo mouse model, bronchoalveolar lavage fluid antitryptic activity assay, oxidative stress markers American journal of physiology. Lung cellular and molecular physiology Medium 11435216
2003 SLPI-deficient (SLPI-/-) mice show increased mortality from LPS-induced endotoxin shock. Mechanistically, SLPI-/- macrophages produce higher IL-6 and HMGB1 and show greater NF-κB activity after LPS treatment. SLPI-/- B cells show more proliferation and IgM production after LPS, demonstrating that endogenous SLPI attenuates NF-κB-mediated inflammatory responses. SLPI knockout mouse model, LPS challenge, macrophage culture, ELISA for cytokines, NF-κB reporter assay, B cell proliferation assay The Journal of experimental medicine High 12615907
2004 SLPI interacts physically with platelet-restricted β1-tubulin, discovered by yeast two-hybrid screen of megakaryocyte cDNAs. In megakaryocytes and platelets, a fraction of SLPI co-localizes along peripheral microtubules in a β1-tubulin-dependent manner (lost in β1-tubulin-/- platelets and upon cold-induced MT disruption). SLPI is released upon platelet activation and its elastase-inhibitory activity is reduced in the absence of β1-tubulin, suggesting regulated anti-proteolytic function at platelet activation. Yeast two-hybrid screen, immunofluorescence, subcellular fractionation, platelet activation assay, β1-tubulin knockout mouse Blood High 15315966
2005 SLPI's suppression of macrophage LPS responses (NO and TNF production) is independent of its anti-protease activity. Single amino acid substitution mutants of SLPI (M73G, M73F, M73E, M73K) that selectively lose elastase and/or chymotrypsin inhibitory activity still suppress LPS responses similarly to wild-type SLPI. Truncated forms containing only the N-terminus or C-terminus are individually sufficient to confer LPS inhibition. Site-directed mutagenesis of SLPI active site, stable transfection of RAW264.7 macrophages, LPS stimulation assay, NO and TNF measurement Biochimica et biophysica acta High 16112212
2005 HIV-1-mediated stimulation of SLPI expression and production in oral epithelial cells occurs at the transcriptional level, is dose- and time-dependent, is induced by heat-inactivated and infectious virus equally, and does not depend on cellular infection. The stimulatory effect is specifically induced by HIV-1 and SIV envelope glycoproteins (gp120), not other viral proteins. Real-time RT-PCR, ELISA, heat-inactivated virus controls, purified retroviral protein experiments, primary oral epithelial cells Journal of virology Medium 15858026
2005 Induction of SLPI in macrophages by Mycobacterium tuberculosis depends on TLR2 but not TLR4 or MyD88. Macrophages from TLR2-/- mice failed to upregulate SLPI in response to heat-killed M. tuberculosis, while TLR4-/- and MyD88-/- macrophages responded normally, identifying a TLR2-dependent, MyD88-independent signaling pathway for SLPI induction. Macrophages from TLR2-/-, TLR4-/-, MyD88-/- knockout mice, real-time PCR and ELISA for SLPI expression Immunology High 16236128
2005 H3-K4 trimethylation across the SLPI coding region is enhanced by IL-1β stimulation and correlates with increased RNA polymerase II recruitment to the SLPI gene. The methylase inhibitor 5-azacytidine attenuates both H3-K4 trimethylation and RNA Pol II recruitment, reducing SLPI mRNA and protein levels, demonstrating that histone H3-K4 methylation regulates SLPI transcriptional induction. Chromatin immunoprecipitation (ChIP), Western blot, SLPI promoter reporter assay, 5-azacytidine pharmacological inhibition Biochemical and biophysical research communications Medium 15845363
2007 Epithelial cell-derived SLPI restrains B cell immunoglobulin class switching by inhibiting AID induction in B cells. SLPI acts as a homeostatic brake on Toll-like receptor-induced class switching in tonsillar B cells. Human tonsillar explant cultures, B cell-epithelial co-culture experiments, AID measurement, immunoglobulin class-switching assays, SLPI blocking experiments Nature immunology High 17259987
2007 SLPI suppresses cancer cell invasion in vitro while promoting blood-borne metastasis via an invasion-independent pathway. Overexpression of SLPI in mammary tumor cells induced sinusoidal vasculature and endothelial-coated tumor emboli in vivo, associated with SLPI's anti-migratory effect on endothelial cells. SLPI inhibited migration of both tumor cells and HUVECs through Matrigel. SLPI gene transfection into MCH66 mouse mammary tumor cells, in vivo tumor implantation, Matrigel invasion/migration assays, in vivo angiogenesis assay The Journal of pathology Medium 17455170
2008 SLPI is synthesized in myelocytes and co-localizes with lactoferrin in secondary granules of neutrophils, as determined by subcellular fractionation. SLPI is co-released with lactoferrin within minutes of neutrophil activation, establishing SLPI as a secondary granule protein in PMNs. Microarray expression profiling of bone marrow populations, immunostaining of bone marrow cells, subcellular fractionation, exocytosis assay Journal of leukocyte biology High 18285402
2008 NE-mediated decrease in SLPI in cell culture supernatants is a passive, charge-dependent phenomenon. Theoretical molecular modeling showed that the NE-SLPI complex has a greater positive charge than complexes of SLPI with other proteinases (trypsin, tryptase), correlating with the selective ability of NE and cathepsin G (but not other proteinases) to reduce secreted SLPI levels by promoting complex binding to negatively-charged cell membranes. Respiratory epithelial cell culture, ELISA, synthetic NE inhibitor controls, theoretical molecular modeling of charge Respiratory research Medium 18699987
2008 SLPI plays a crucial role in early myocardial performance after ischemia/reperfusion in cardiac transplantation. SLPI-/- hearts showed profoundly impaired early contractility after cold ischemia, associated with high intra-graft protease expression. rSLPI added to preservation solution (but not systemic administration) restored normal myocardial contraction. Intra-graft SLPI inversely correlated with protease levels and TGF-β expression. SLPI-/- mouse heterotopic cardiac transplantation model, recombinant SLPI administration, myocardial performance assessment, histology, ELISA for TNF-α, TGF-β, protease levels American journal of transplantation Medium 18294346
2008 SLPI promotes proliferation and oligodendroglial differentiation of adult neural stem cells. Recombinant SLPI treatment increased cell proliferation (BrdU incorporation), upregulated cyclin D1, suppressed HES1, and prevented degradation of IκBα in neural stem cells, suggesting NF-κB pathway inhibition as a mechanism underlying oligodendroglial differentiation. Adult neural stem cell culture, recombinant SLPI treatment, BrdU incorporation, real-time PCR for cyclin D1 and HES1, Western blot for IκBα, immunofluorescence Journal of neuroinflammation Medium 18501024
2010 Protein disulfide isomerase (PDI) overexpression enhances SLPI folding in Pichia pastoris, increasing SLPI yield >5-fold and enhancing its specific anti-protease activity. Mass spectrometry confirmed a greater number of disulfide bonds in PDI-overexpression-derived SLPI, demonstrating that proper disulfide bond formation is required for SLPI biological activity. Recombinant protein expression in Pichia pastoris, mass spectrometry disulfide bond analysis, anti-protease activity assay Biochemical and biophysical research communications Medium 20971072
2011 SLPI is a substrate for tissue transglutaminase (type 2) and plasma transglutaminase (factor XIIIa), which covalently cross-link it to fibronectin and elastin. Cross-linked SLPI retains its ability to inhibit elastase and cathepsin G. Mass spectrometry identified transglutamination sites: reactive lysine and glutamine residues are located predominantly in SLPI's N-terminal domain. In vitro transglutaminase cross-linking assay, mass spectrometry of tryptic digests, enzymatic activity assay of cross-linked SLPI PloS one High 21687692
2011 TSLP signaling through TSLP receptor on intestinal epithelial cells (non-hematopoietic cells) induces SLPI expression, and this SLPI induction is required for mucosal healing after DSS-induced colitis. TSLP-deficient mice failed to recover from colitis and showed increased neutrophil elastase (NE) activity and reduced SLPI; pharmacological NE inhibition or rSLPI treatment rescued mortality in Tslp-/- mice. Tslp-/- mouse model, DSS colitis, rSLPI treatment, NE pharmacological inhibitor, bone marrow chimera experiments (TSLPR on non-hematopoietic cells) Immunity High 21820333
2011 SLPI promotes tumor invasion in ovarian cancer by inducing MMP-9 transcription and protein production independent of its serine protease inhibitory activity. A protease-inhibitor-null SLPI mutant (F-SLPI) similarly induces MMP-9 transcription and increases invasion. Wild-type SLPI additionally inhibits plasmin activity and MMP-9 activation, yielding net increased MMP-9 activity. SLPI and MMP-9 are strongly correlated in serous ovarian cancers. Stable HEYA8 ovarian cancer transfectants with wild-type and protease-inhibitor-null SLPI, invasion assay, MMP-9 transcription/protein/activity assay, plasmin activity assay, xenograft model, tissue microarray Gynecologic oncology High 21676452
2011 SLPI is produced in human mast cells. Double-immunolabeling showed SLPI coexists with tryptase (60%) and chymase (37%)-containing mast cells, and in situ hybridization confirmed SLPI mRNA expression in all mast cells, suggesting SLPI acts as a local regulator of mast cell protease activity. Double immunolabeling, in situ hybridization Biological chemistry Medium 10355635
2012 SLPI inhibits regulatory T cell differentiation. In vitro addition of SLPI to naive human CD4+ T cell cultures significantly decreased the number of functional FoxP3+ CD25hi CD4+ regulatory T cells. Recombinant TGF-β neutralized SLPI's inhibitory effect on Treg differentiation, placing SLPI upstream of TGF-β in this pathway. In vivo, SLPI neutralization in EAE increased serum TGF-β and FoxP3+ T cells. Human CD4+ T cell culture with recombinant SLPI, SLPI-neutralizing antibody in EAE mouse and rat model, flow cytometry, ELISA for TGF-β, TGF-β rescue experiment BMC neuroscience Medium 22436018
2012 Nrf2 transcriptionally regulates SLPI expression in nasal epithelial cells. Sulforaphane (SFN, an Nrf2 activator) significantly enhanced SLPI secretion in vitro, and this effect was significantly reduced by Nrf2-specific shRNA knockdown, establishing Nrf2 as a direct regulator of SLPI transcription. Nasal lavage fluid ELISA after sulforaphane ingestion, differentiated primary nasal epithelial cells, Nrf2 shRNA knockdown, SLPI ELISA Respiratory medicine Medium 23195333
2013 SLPI controls myeloid cell proliferation, differentiation, and cell cycle. Downregulation of SLPI with shRNA in CD34+ hematopoietic progenitors reduced myeloid differentiation, caused cell-cycle arrest, and elevated apoptosis. Mechanistically, SLPI knockdown upregulated NF-κB and reduced phospho-ERK1/2-mediated phosphorylation/activation of LEF-1 transcription factor. Wild-type NE (but not mutant forms) upregulated SLPI, establishing reciprocal NE-SLPI regulation. shRNA knockdown of SLPI in CD34+ bone marrow progenitors, neutrophil elastase transduction (wild-type and mutant), flow cytometry for differentiation/apoptosis/cell-cycle, Western blot for NF-κB and p-ERK1/2, microarray analysis Blood High 24352879
2013 STAT1 transcriptionally regulates SLPI expression in airway epithelial cells. STAT1 promoter reporter assays and chromatin immunoprecipitation confirmed STAT1 binding to the SLPI promoter. Stat1-/- mice showed reduced pulmonary Slpi protein. Smokers have increased STAT1 mRNA/protein in nasal epithelial cells, explaining their increased SLPI expression. SLPI promoter reporter assays, chromatin immunoprecipitation (ChIP), stat1-/- mouse model, Western blot and RT-PCR American journal of physiology. Lung cellular and molecular physiology High 24285265
2014 SLPI functions as a novel inhibitor of plasminogen activation through its interaction with annexin A2, with concomitant reduction in plasmin generation by macrophages and OSCC cell lines. In vitro, SLPI blocked protease-dependent tumor cell migration. Co-immunoprecipitation of SLPI with annexin A2, plasmin generation assay with macrophages and cell lines, in vitro invasion assay The American journal of pathology Medium 21641406
2014 SLPI exerts antifungal activity against Candida albicans, including reducing secreted serine proteinase activity by 48.8%, reducing adhesion to mammalian cells by 60.1%, reducing cell surface mannoprotein expression, and causing ultrastructural changes (membrane-like structures in cytoplasm). Flow cytometry suggested specific SLPI binding sites on the yeast surface. MIC determination, serine proteinase activity assay, flow cytometry for surface receptors and mannoproteins, adhesion assay, transmission electron microscopy Archives of oral biology Medium 24907522
2015 IFN-γ inversely regulates SLPI expression, defining a dysregulated IFN-γ/SLPI axis in severe asthma. In a severe asthma mouse model, forced SLPI expression decreased airway hyperresponsiveness (AHR) independent of corticosteroids, and combining SLPI with CS further reduced AHR. Pathway analysis linked IFN-γ to SLPI suppression, confirmed in both SA patients and the mouse model. Computer-assisted pathway analysis, severe asthma mouse model with Ifng-/- and Il17ra-/- mice, adenoviral SLPI overexpression, airway hyperresponsiveness measurement (AHR), BAL analysis from human SA and MMA patients The Journal of clinical investigation High 26121748
2015 SLPI inhibits NET (neutrophil extracellular trap) formation in human neutrophils in a manner partially dependent on its NE-inhibitory activity. SLPI inhibits histone H4 (H4) cleavage during NET formation. SLPI-/- mouse neutrophils are more efficient at generating NETs than WT neutrophils in vitro and in experimental psoriasis in vivo. Endogenous SLPI co-localizes with NE in the nucleus of human neutrophils both in vitro and in psoriatic skin. Human neutrophil NET assay with recombinant SLPI, SLPI-/- mouse neutrophils, histone H4 cleavage assay, immunofluorescence co-localization, experimental psoriasis model Journal of leukocyte biology High 25917460
2017 SLPI physically interacts with the retinoblastoma tumor suppressor protein (Rb) and releases FoxM1 from the Rb-FoxM1 complex, potentially activating FoxM1 target genes involved in breast cancer metastasis. SLPI secretion was identified as a target of a novel compound (C74) that inhibits SLPI secretion, reducing tumor growth and lung metastasis. High-throughput screening for SLPI secretion inhibitors, co-immunoprecipitation of SLPI with Rb, FoxM1 complex disruption assay, orthotopic 4T1 mouse tumor model Oncotarget Medium 29312532
2017 SLPI promotes osteoblast focal adhesion on titanium surfaces. Recombinant SLPI treatment of MC3T3-E1 cells on titanium increased actin stress fibers, paxillin expression, FAK phosphorylation, and ERK1/2 phosphorylation through Grb2-Ras signaling, establishing SLPI as an activator of integrin-FAK-ERK signaling for cell adhesion. MC3T3-E1 osteoblast culture on titanium, recombinant SLPI treatment, immunofluorescence for actin/paxillin, Western blot for FAK, Grb2, Ras, ERK1/2 phosphorylation Journal of nanoscience and nanotechnology Low 26328330
2019 SLPI dose-dependently inhibits ATP-mediated inflammasome activation and IL-1β release in human monocytic cells without affecting pro-IL-1β mRNA induction by LPS. The mechanism involves activation of calcium-independent phospholipase A2β (iPLA2β), release of a low-molecular-mass mediator, signaling through nicotinic acetylcholine receptor subunits α7, α9, α10, and Src kinase activation, resulting in inhibition of ATP-induced caspase-1 activation. SLPI does not directly modulate P2X7 receptor ion channel function in Xenopus oocytes but inhibits ATP-induced ion currents in human U937 cells. Human monocytic cell culture, ELISA for IL-1β, RT-PCR for pro-IL-1β, specific inhibitors and siRNA for iPLA2β, nicotinic receptor subunit siRNA, caspase-1 activity assay, Xenopus oocyte electrophysiology Frontiers in immunology Medium 31019507
2019 Mecp2 binds to the Slpi promoter and negatively regulates Slpi expression in adipose tissue, thereby suppressing adipose tissue browning. Fat-specific Mecp2 knockout mice show upregulated Slpi and enhanced browning; knockdown of Slpi in inguinal WAT of Mecp2 KO mice prevented cold-induced browning. Recombinant SLPI treatment reduced HFD-induced obesity by enhancing browning. ChIP for Mecp2 binding to Slpi promoter, fat-specific Mecp2 knockout mouse, RNA-seq, Slpi knockdown in vivo, recombinant SLPI treatment in vivo Diabetes High 31597640
2019 Endothelial cell-derived SLPI protects cardiomyocytes against ischemia/reperfusion injury via a paracrine mechanism. Co-culture of SLPI-overexpressing endothelial cells with cardiomyocytes or conditioned medium treatment enhanced cardiomyocyte viability, reduced intracellular ROS, decreased Bax/Bcl-2 ratio and caspase-3/8 levels, and activated p38 MAPK and Akt survival kinases. Stable endothelial cell overexpression of SLPI, co-culture and conditioned medium experiments, cell viability assay, ROS measurement, Western blot for apoptosis markers and signaling kinases Biomolecules Medium 31683729
2008 Only chymase, among all SLPI-interacting proteases, uniquely cleaves SLPI at a specific site. In vitro enzymatic assays using Western blot and LC/MS demonstrated cleavage products that remain coupled via disulfide bonds under non-reducing conditions. Cleaved SLPI (cSLPI) was detected in human saliva and correlated with allergic symptoms, establishing cSLPI as a biomarker of chymase activity. In vitro enzymatic cleavage assay with multiple proteases, Western blot, LC/MS, analysis of human saliva samples, chymase inhibitor controls Biological chemistry Medium 18713008
2023 Excessive dietary iron promotes colorectal tumorigenesis through upregulation of SLPI in intestinal epithelial cells, which in turn activates the MAPK signaling pathway as a pro-tumorigenic mechanism. This was demonstrated in multiple mouse colorectal cancer models with gut microbiota manipulation. Multiple mouse colorectal cancer models with dietary iron manipulation, gut microbiota analysis, Akkermansia supplementation, SLPI measurement and functional pathway analysis Gut microbes Medium 37312410

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 High IFN-γ and low SLPI mark severe asthma in mice and humans. The Journal of clinical investigation 332 26121748
1994 Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. American journal of respiratory cell and molecular biology 249 7946401
2007 Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nature immunology 225 17259987
1986 The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease). Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red Sea turtle proteinase inhibitor. FEBS letters 180 3485543
2007 Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family. Biochimie 150 17964057
1997 Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-I. Oral diseases 134 9456660
2015 Secretory leukocyte protease inhibitor (SLPI), a multifunctional protein in the host defense response. Cytokine & growth factor reviews 113 26718149
2003 Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice. The Journal of experimental medicine 110 12615907
2000 Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins. American journal of physiology. Lung cellular and molecular physiology 97 10645890
2011 Thymic stromal lymphopoetin-induced expression of the endogenous inhibitory enzyme SLPI mediates recovery from colonic inflammation. Immunity 95 21820333
1998 Induction of SLPI (ALP/HUSI-I) in epidermal keratinocytes. The Journal of investigative dermatology 95 9856807
1988 Human mucus proteinase inhibitor (human MPI). Human seminal inhibitor I (HUSI-I), antileukoprotease (ALP), secretory leukocyte protease inhibitor (SLPI). Biological chemistry Hoppe-Seyler 95 3060147
2011 SLPI and elafin: multifunctional antiproteases of the WFDC family. Biochemical Society transactions 88 21936829
2015 The inhibitory effect of secretory leukocyte protease inhibitor (SLPI) on formation of neutrophil extracellular traps. Journal of leukocyte biology 78 25917460
1999 Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle. Molecular human reproduction 77 10381821
2021 Secretory Leukocyte Protease Inhibitor (SLPI) in mucosal tissues: Protects against inflammation, but promotes cancer. Cytokine & growth factor reviews 69 33602652
2008 The lower genital tract microbiota in relation to cytokine-, SLPI- and endotoxin levels: application of checkerboard DNA-DNA hybridization (CDH). APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 62 18397461
2003 The secretory leukoprotease inhibitor (SLPI) promoter for ovarian cancer gene therapy. The journal of gene medicine 54 12692864
2000 Regulation of secretory leukocyte proteinase inhibitor (SLPI) production by human bronchial epithelial cells: increase of cell-associated SLPI by neutrophil elastase. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 53 10979241
2005 Human immunodeficiency virus type 1 stimulates the expression and production of secretory leukocyte protease inhibitor (SLPI) in oral epithelial cells: a role for SLPI in innate mucosal immunity. Journal of virology 51 15858026
2013 A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation. Blood 48 24352879
2007 Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma. Respiratory medicine 47 17574828
2011 Secretory leukocyte protease inhibitor (SLPI) expression and tumor invasion in oral squamous cell carcinoma. The American journal of pathology 46 21641406
1986 Inhibition of mast cell chymase by eglin c and antileukoprotease (HUSI-I). Indications for potential biological functions of these inhibitors. Biological chemistry Hoppe-Seyler 46 3530282
2003 Up-regulation of secretory leukocyte protease inhibitor (SLPI) in the brain after ischemic stroke: adenoviral expression of SLPI protects brain from ischemic injury. Molecular pharmacology 45 14500739
2001 Human SLPI inactivation after cigarette smoke exposure in a new in vivo model of pulmonary oxidative stress. American journal of physiology. Lung cellular and molecular physiology 45 11435216
2008 Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis. Journal of neuroinflammation 44 18501024
2005 Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease function. Biochimica et biophysica acta 44 16112212
2017 MIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms. American journal of physiology. Renal physiology 40 28539339
2002 The presence of elafin, SLPI, IL1-RA and STNFalpha RI in head and neck squamous cell carcinomas and their relation to the degree of tumour differentiation. Mediators of inflammation 39 11926597
2007 The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion but promotes blood-borne metastasis via an invasion-independent pathway. The Journal of pathology 37 17455170
2002 The expression of secretory leukocyte protease inhibitor (SLPI) in the fallopian tube: SLPI protects the acrosome reaction of sperm from inhibitory effects of elastase. Human reproduction (Oxford, England) 35 12351521
2023 Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis. Gut microbes 34 37312410
2019 Fat-Specific Knockout of Mecp2 Upregulates Slpi to Reduce Obesity by Enhancing Browning. Diabetes 34 31597640
2022 FAPhigh α-SMAlow cancer-associated fibroblast-derived SLPI protein encapsulated in extracellular vesicles promotes ovarian cancer development via activation of PI3K/AKT and downstream signaling pathways. Molecular carcinogenesis 33 35801406
2008 The secretory leukocyte protease inhibitor (SLPI) and the secondary granule protein lactoferrin are synthesized in myelocytes, colocalize in subcellular fractions of neutrophils, and are coreleased by activated neutrophils. Journal of leukocyte biology 33 18285402
2011 War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection. Biochemical Society transactions 32 21936827
2020 Differences in Staining for Neutrophil Elastase and its Controlling Inhibitor SLPI Reveal Heterogeneity among Neutrophils in Psoriasis. The Journal of investigative dermatology 31 31945345
2017 Secretory leukocyte protease inhibitor (SLPI) as a potential target for inhibiting metastasis of triple-negative breast cancers. Oncotarget 31 29312532
2005 Altered expression of CLC, DSG3, EMP3, S100A2, and SLPI in corneal epithelium from keratoconus patients. Cornea 31 16015083
1998 Secretory leukocyte protease inhibitor (SLP) concentrations in seminal plasma: SLPI restores sperm motility reduced by elastase. Molecular human reproduction 31 9809675
2019 Androgen receptor suppresses prostate cancer metastasis but promotes bladder cancer metastasis via differentially altering miRNA525-5p/SLPI-mediated vasculogenic mimicry formation. Cancer letters 30 31843555
2004 Expression of human kallikrein 7 (hK7/SCCE) and its inhibitor antileukoprotease (ALP/SLPI) in uterine endocervical glands and in cervical adenocarcinomas. Oncology reports 30 15492784
2002 Inhibitory function of secretory leukocyte proteinase inhibitor (SLPI) in human saliva is HIV-1 specific and varies with virus tropism. Oral diseases 29 12108760
2023 Secretory leukocyte protease inhibitor (SLPI) in cancer pathophysiology: Mechanisms of action and clinical implications. Pathology, research and practice 27 37356220
2019 SLPI Inhibits ATP-Mediated Maturation of IL-1β in Human Monocytic Leukocytes: A Novel Function of an Old Player. Frontiers in immunology 27 31019507
2017 SLPI promotes the gastric cancer growth and metastasis by regulating the expression of P53, Bcl-2 and Caspase-8. European review for medical and pharmacological sciences 27 28429358
2008 The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 27 18294346
1993 Inhibition by recombinant SLPI and half-SLPI (Asn55-Ala107) of elastase and cathepsin G activities: consequence for neutrophil-platelet cooperation. British journal of pharmacology 27 8097952
2011 Paracrine SLPI secretion upregulates MMP-9 transcription and secretion in ovarian cancer cells. Gynecologic oncology 26 21676452
2020 LCN2 Mediated by IL-17 Affects the Proliferation, Migration, Invasion and Cell Cycle of Gastric Cancer Cells by Targeting SLPI. Cancer management and research 25 33364832
2010 An improved method for enhanced production and biological activity of human secretory leukocyte protease inhibitor (SLPI) in Pichia pastoris. Biochemical and biophysical research communications 25 20971072
2011 SLPI and inflammatory lung disease in females. Biochemical Society transactions 24 21936826
2004 Interactions between the megakaryocyte/platelet-specific beta1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions. Blood 24 15315966
1990 The elimination of secretory leukocyte protease inhibitor (SLPI) after intravenous injection in dog and man. Scandinavian journal of clinical and laboratory investigation 24 2293334
2019 Endothelial-Cell-Derived Human Secretory Leukocyte Protease Inhibitor (SLPI) Protects Cardiomyocytes against Ischemia/Reperfusion Injury. Biomolecules 23 31683729
2014 The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma. Cancer letters 23 25462861
2010 Differential effects of periopathogens on host protease inhibitors SLPI, elafin, SCCA1, and SCCA2. Journal of oral microbiology 23 21523231
2005 Induction of macrophage-derived SLPI by Mycobacterium tuberculosis depends on TLR2 but not MyD88. Immunology 23 16236128
2012 Sulforaphane induces SLPI secretion in the nasal mucosa. Respiratory medicine 22 23195333
2015 Cervical Expression of Elafin and SLPI in Pregnancy and Their Association With Preterm Labor. American journal of reproductive immunology (New York, N.Y. : 1989) 21 25559229
2014 Effect of the secretory leucocyte proteinase inhibitor (SLPI) on Candida albicans biological processes: a therapeutic alternative? Archives of oral biology 21 24907522
2014 Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E-cadherin, induces β-catenin re-localisation and triggers apoptosis-related events in breast cancer cells. Biology of the cell 21 25039920
2009 Temporal induction of secretory leukocyte protease inhibitor (SLPI) in odontoblasts by lipopolysaccharide and wound infection. Journal of endodontics 21 19567322
2007 A secretory leukocyte proteinase inhibitor (SLPI)-like protein from Litopenaeus vannamei haemocytes. Fish & shellfish immunology 21 17664073
1999 Identification of SLPI (secretory leukocyte protease inhibitor) in human mast cells using immunohistochemistry and in situ hybridisation. Biological chemistry 21 10355635
2017 Secretory Leukoprotease Inhibitor (Slpi) Expression Is Required for Educating Murine Dendritic Cells Inflammatory Response Following Quercetin Exposure. Nutrients 20 28684695
2011 Secretory leukocyte protease inhibitor (SLPI) is, like its homologue trappin-2 (pre-elafin), a transglutaminase substrate. PloS one 20 21687692
2008 Neutrophil elastase reduces secretion of secretory leukoproteinase inhibitor (SLPI) by lung epithelial cells: role of charge of the proteinase-inhibitor complex. Respiratory research 20 18699987
2009 Expression and characterization of recombinant human secretory leukocyte protease inhibitor (SLPI) protein from Pichia pastoris. Protein expression and purification 19 19505578
1999 The effect of immediate-hypersensitivity reactions on the level of SLPI, granulocyte elastase, alpha1-antitrypsin, and albumin in nasal secretions, by the method of unilateral antigen challenge. Allergy 19 10485390
1998 Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes. American journal of respiratory cell and molecular biology 19 9843921
2025 A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions. Nature aging 18 40442321
2013 The role of the antileukoprotease SLPI in smoking-induced human papillomavirus-independent head and neck squamous cell carcinomas. International journal of cancer 18 23996702
2012 Higher SLPI expression, lower immune activation, and increased frequency of immune cells in a cohort of Colombian HIV-1 controllers. Journal of acquired immune deficiency syndromes (1999) 18 22240462
1999 Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation. Oncogene 18 10498899
2022 SLPI suppresses hepatocellular carcinoma progression via endoplasmic reticulum stress induced apoptosis. International journal of biological sciences 17 34975323
2013 Regulation and activity of secretory leukoprotease inhibitor (SLPI) is altered in smokers. American journal of physiology. Lung cellular and molecular physiology 16 24285265
2011 Novel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet. Journal of inflammation (London, England) 16 21356117
2008 SLPI prevents cytokine release in mite protease-exposed conjunctival epithelial cells. Biochemical and biophysical research communications 15 19103172
2020 Targeting secretory leukocyte protease inhibitor (SLPI) inhibits colorectal cancer cell growth, migration and invasion via downregulation of AKT. PeerJ 14 32742768
2012 Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma. Cancer gene therapy 14 22388454
2012 Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis. BMC neuroscience 14 22436018
2008 Cleaved SLPI, a novel biomarker of chymase activity. Biological chemistry 14 18713008
2021 Reduced ELANE and SLPI expression compromises dental pulp cell activity. Cell proliferation 13 34580954
2014 Aberrant host defense against Leishmania major in the absence of SLPI. Journal of leukocyte biology 13 25030421
2005 5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene. Biochemical and biophysical research communications 13 15845363
2014 Secretory Leukocyte Protease Inhibitor (SLPI): Emerging Roles in CNS Trauma and Repair. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 12 25118190
2006 Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases. Biological chemistry 12 16913839
2023 Inhibition of secretory leukocyte protease inhibitor (SLPI) promotes the PUMA-mediated apoptosis and chemosensitivity to cisplatin in colorectal cancer cells. Discover oncology 11 36595102
2021 Overexpression of secretory leukocyte peptidase inhibitor (SLPI) does not modulate experimental osteoarthritis but may be a biomarker for the disease. Osteoarthritis and cartilage 11 33485930
2015 SLPI knockdown induced pancreatic ductal adenocarcinoma cells proliferation and invasion. Cancer cell international 11 25954138
2024 Isorhamnetin ameliorates cisplatin-induced acute kidney injury in mice by activating SLPI-mediated anti-inflammatory effect in macrophage. Immunopharmacology and immunotoxicology 10 38466121
2022 Simultaneous and ultra-sensitive SERS detection of SLPI and IL-18 for the assessment of donor kidney quality using black phosphorus/gold nanohybrids. Optics express 10 35209305
2021 SLPI in periodontal Ligament is not sleepy during biophysical force-induced tooth movement. Journal of clinical periodontology 10 33370451
2016 Salivary secretory leukocyte protease inhibitor (SLPI) and head and neck cancer: The Cancer Prevention Study II Nutrition Cohort. Oral oncology 10 27016010
2015 Secretory Leukocyte Protease Inhibitor (SLPI) Increases Focal Adhesion in MC3T3 Osteoblast on Titanium Surface. Journal of nanoscience and nanotechnology 10 26328330
2013 Anti-tumor effect of SLPI on mammary but not colon tumor growth. Journal of cellular physiology 10 22767220
2011 Mucosal Progranulin expression is induced by H. pylori, but independent of Secretory Leukocyte Protease Inhibitor (SLPI) expression. BMC gastroenterology 10 21612671
1999 Production of secretory leucocyte protease inhibitor (SLPI) in human pancreatic beta-cells. Mediators of inflammation 10 10704052

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