Affinage

CCL18

C-C motif chemokine 18 · UniProt P55774

Length
89 aa
Mass
9.8 kDa
Annotated
2026-04-28
100 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL18 is a primate-specific CC-chemokine that functions as a pleiotropic mediator of immune regulation, tissue fibrosis, and cancer metastasis. It signals through two validated receptors—PITPNM3 (Nir1) and CCR8—to activate intracellular calcium flux, Pyk2/Src kinase cascades, NF-κB, PI3K/Akt, and ARF6 pathways, which collectively drive integrin clustering, cytoskeletal reorganization, epithelial-mesenchymal transition, and cancer cell invasion (PMID:21481794, PMID:23999500, PMID:24142406, PMID:26449829, PMID:35399607). In fibroblasts, CCL18 stimulates collagen production through PKCα/ERK2/Sp1 signaling independently of autocrine TGF-β, and in vivo it promotes T lymphocyte-dependent pulmonary fibrosis (PMID:16601239, PMID:16021625, PMID:16868995). CCL18 also attenuates leukocyte recruitment by displacing heparin-bound chemokines from glycosaminoglycans on endothelial surfaces, and its own expression in tumor-associated macrophages is regulated by IL-10, STAT6 signaling, and H3K18 lactylation at its promoter (PMID:23951310, PMID:12646652, PMID:39010846).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 Medium

    Determining CCL18's evolutionary origin resolved why it has lymphocyte-directed chemotactic activity distinct from its closest paralog MIP-1α despite high sequence identity.

    Evidence BAC clone genomic analysis showing CCL18 arose by fusion of two MIP-1α-like genes on 17q11.2

    PMID:10049593

    Open questions at the time
    • No receptor identified at this stage
    • Functional divergence from MIP-1α not tested beyond chemotaxis
  2. 2003 Medium

    Establishing that CCL18 is constitutively produced by immature dendritic cells and suppressed upon maturation positioned it as a tolerogenic/anti-inflammatory chemokine, with IL-10 and vitamin D3 as key inducers.

    Evidence Cytokine stimulation panel of monocyte-derived DCs with ELISA and chemotaxis assays

    PMID:12646652

    Open questions at the time
    • Receptor mediating DC chemotaxis unknown
    • In vivo relevance of DC-derived CCL18 not tested
  3. 2006 Medium

    Dissecting the pro-fibrotic signaling cascade showed that CCL18 stimulates collagen production in lung fibroblasts through calcium/PKCα/ERK2/Sp1 and basal Smad3, independent of autocrine TGF-β, and that in vivo CCL18 drives T cell-dependent pulmonary collagen deposition.

    Evidence Dominant-negative PKCα/ERK2/Sp1/Smad3 mutants, pharmacological inhibitors, adenoviral CCL18 delivery in mouse lungs with anti-lymphocyte serum depletion

    PMID:16021625 PMID:16601239 PMID:16868995

    Open questions at the time
    • Fibroblast receptor for CCL18 not identified
    • Relationship between direct fibroblast stimulation and T cell-mediated collagen deposition unclear
  4. 2011 High

    Identification of PITPNM3 as a functional CCL18 receptor on breast cancer cells established the mechanistic basis for TAM-derived CCL18 driving integrin clustering, ECM adherence, and tumor invasiveness.

    Evidence Co-IP, calcium signaling, PITPNM3 siRNA knockdown, invasion assays, and xenograft mouse models

    PMID:21481794

    Open questions at the time
    • PITPNM3 structure-function relationship with CCL18 unresolved
    • Whether PITPNM3 is the sole cancer-relevant receptor unclear
  5. 2013 High

    Discovery that CCR8 serves as a second high-affinity CCL18 receptor, and that CCL18 independently inhibits chemokine-mediated leukocyte recruitment by displacing GAG-bound chemokines, revealed dual receptor-dependent and receptor-independent immunomodulatory mechanisms.

    Evidence Competitive binding, calcium flux, chemotaxis on CCR8-transfected cells, Ccr8-KO Th2 cells; Schild plot analysis and GAG displacement assays

    PMID:23951310 PMID:23999500

    Open questions at the time
    • Relative contribution of PITPNM3 vs CCR8 in different cell types not systematically compared
    • GAG displacement mechanism not validated in vivo
  6. 2014 Medium

    Elucidation of the Pyk2→Src kinase relay downstream of PITPNM3 established how CCL18 receptor engagement translates into integrin β1 clustering and cytoskeletal-dependent cell motility.

    Evidence Co-IP of Pyk2 with PITPNM3, immunofluorescence showing Pyk2 membrane translocation, Src activation by Western blot, invasion/adherence assays

    PMID:24142406

    Open questions at the time
    • No structural data on PITPNM3-Pyk2 interface
    • Pyk2 phosphorylation site specificity not mapped
  7. 2015 Medium

    Demonstration that CCL18/PITPNM3 activates NF-κB (IKK/IκBα/p65) and N-Ras/ERK/PI3K/Lin28b pathways, and that CCL18 sustains its own signaling via miR-98/miR-27b suppression, broadened the downstream effector landscape to include EMT transcriptional programs.

    Evidence PITPNM3 siRNA in HCC cells; miRNA profiling, pathway inhibitors, overexpression/knockdown of miR-98 and miR-27b in breast cancer cells

    PMID:26244871 PMID:26449829

    Open questions at the time
    • Positive feedback loop duration and in vivo relevance not established
    • NF-κB and miRNA arms not tested for cross-talk
  8. 2016 Medium

    Identification of ELMO1/RAC1 as effectors of CCL18/Nir1 signaling in NSCLC and confirmation of Pyk2 in ovarian cancer migration generalized the Pyk2-integrin and RAC1-cytoskeleton axes across tumor types.

    Evidence ELMO1 siRNA, RAC1 activation assays in NSCLC; Pyk2 siRNA/overexpression with CCL18 blocking antibody in ovarian cancer

    PMID:26756176 PMID:27613122

    Open questions at the time
    • Whether ELMO1 and Pyk2 operate in the same or parallel branches not determined
    • Upstream adapter linking PITPNM3 to RAC1/ELMO1 unknown
  9. 2018 Medium

    Discovery that CCL18 triggers PCAF-mediated acetylation of ACAP4 and ezrin revealed a post-translational regulatory layer governing ARF6 membrane cycling and ezrin conformational dynamics essential for cell migration.

    Evidence Mass spectrometry of acetylation sites, PCAF co-IP, acetylation-mimicking/non-acetylatable mutants, AFM structural analysis, migration assays

    PMID:30395269 PMID:31638145

    Open questions at the time
    • How CCL18 signal activates PCAF acetyltransferase not known
    • ACAP4/ezrin acetylation not validated in vivo
  10. 2022 Medium

    Convergent studies established CCL18 as a master organizer of the tumor microenvironment: it converts normal fibroblasts to chemoresistance-promoting CAFs via NF-κB/IL-6/IL-8, signals through CCR8-ACP5 in glioma, and propagates invasion via exosomal miR-760/ARF6.

    Evidence Co-culture with anti-CCL18 blocking, xenograft models; humanized brain slice and GBM mouse models; exosome uptake assays with ARF6 knockdown and in vivo metastasis

    PMID:35399607 PMID:35417708 PMID:36418470

    Open questions at the time
    • Whether CAF conversion requires CCR8 or PITPNM3 on fibroblasts not tested
    • Exosomal miR-760 mechanism awaits independent replication
  11. 2024 Medium

    Identification of H3K18 lactylation at the CCL18 promoter in macrophages linked tumor-derived lactate metabolism to epigenetic control of CCL18 transcription, closing a regulatory loop between tumor glycolysis and TAM-mediated immune evasion.

    Evidence ChIP-qPCR for H3K18 lactylation, luciferase reporter, Gpr132 siRNA, anti-CCL18 antibody rescue, xenograft model

    PMID:39010846

    Open questions at the time
    • Genome-wide specificity of lactylation-driven CCL18 regulation not assessed
    • Whether other epigenetic marks cooperate with H3K18la at the CCL18 locus unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CCL18 binding to PITPNM3 versus CCR8, the cell-type-specific partitioning of signaling between these receptors, and whether the GAG-displacement anti-inflammatory function operates in vivo.
  • No crystal or cryo-EM structure of CCL18-receptor complexes
  • No systematic genetic model distinguishing PITPNM3 vs CCR8 contributions in vivo
  • GAG displacement function not validated in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-168256 Immune System 5 R-HSA-1474244 Extracellular matrix organization 3
Partners
ACAP4CCR8ELMO1PCAFPITPNM3PYK2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 CCL18 released by breast tumor-associated macrophages promotes cancer cell invasiveness by triggering integrin clustering and enhancing adherence to extracellular matrix; PITPNM3 was identified as a functional receptor for CCL18 that mediates these effects and activates intracellular calcium signaling. Co-immunoprecipitation, calcium signaling assays, siRNA knockdown of PITPNM3, invasion/migration assays, xenograft mouse models Cancer cell High 21481794
2013 Human chemokine receptor CCR8 is a functional receptor for CCL18; CCL18 induces chemotaxis and calcium flux via CCR8, binds CCR8 with high affinity, causes CCR8 internalization, and cross-desensitizes with CCL1 (the known CCR8 ligand) on Th2 cells. Chemotaxis assays with CCR8-transfected cells, calcium flux assays, competitive binding assays, receptor internalization assays, Ccr8-knockout mouse Th2 cells The Journal of experimental medicine High 23999500
2014 Upon CCL18 binding to PITPNM3, Pyk2 translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating Src kinase; Pyk2 and Src are essential for integrin alpha5/beta1 clustering-dependent adherence, migration, and invasion. Co-immunoprecipitation, immunofluorescence, Western blotting, Boyden chamber assay, adherence assay Journal of cellular biochemistry Medium 24142406
2006 CCL18 stimulates collagen production in pulmonary fibroblasts through a PKCalpha-mediated pathway: CCL18 triggers intracellular calcium increase, leading to PKCalpha phosphorylation and nuclear translocation, ERK2 phosphorylation, and collagen upregulation; this is independent of autocrine TGF-beta. Dominant-negative PKCalpha/ERK2 mutants, pharmacological inhibitor Gö6976, intracellular calcium chelation (BAPTA), collagen promoter reporter constructs, Western blotting American journal of respiratory cell and molecular biology Medium 16601239
2006 CCL18-stimulated collagen upregulation in pulmonary fibroblasts requires Sp1 signaling (phosphorylation, DNA binding, reporter activity) and basal Smad3 activity, but is independent of autocrine TGF-beta. Dominant-negative Sp1 and Smad3 mutants, Sp1-dependent reporter assay, neutralizing anti-TGF-beta antibodies, ALK5 inhibitor, collagen mRNA/protein measurements Journal of cellular physiology Medium 16021625
2015 CCL18 enhances HCC cell migration, invasion, and EMT via PITPNM3-dependent activation of NF-κB signaling (phosphorylation of IKK and IKBα, p65 nuclear translocation); these effects are abrogated by siRNA silencing of PITPNM3. siRNA knockdown of PITPNM3, Western blotting for p65 nuclear translocation and IKK/IKBα phosphorylation, migration/invasion assays Tumour biology Medium 26449829
2016 CCL18 promotes NSCLC cell invasion and migration by binding to receptor Nir1 (PITPNM3), which activates RAC1-dependent cytoskeleton reorganization through ELMO1, and enhances cell adhesion via ELMO1-integrin β1 signaling. CCL18-Nir1 binding assays, RAC1 activation assays, siRNA knockdown of ELMO1, invasion/migration assays Molecular carcinogenesis Medium 26756176
2016 CCL18 from ovarian cancer ascites promotes tumor cell migration via phosphorylation of proline-rich tyrosine kinase 2 (Pyk2); siRNA-mediated downregulation of Pyk2 attenuates ascites- and CCL18-induced cell migration. siRNA knockdown of Pyk2, ectopic Pyk2 expression, Boyden chamber migration assay, CCL18 blocking antibodies, Western blotting for phospho-Pyk2 Molecular cancer Medium 27613122
2022 CCL18 from TAMs activates NF-κB signaling via PITPNM3 in fibroblasts to enhance IL-6 and IL-8 production, converting normal breast-resident fibroblasts into a CD10+GPR77+ chemoresistance-inducing CAF phenotype. Co-culture systems, anti-CCL18 antibody blocking, Western blotting, siRNA/overexpression, in vivo CCL18 intratumoral injection xenograft models Oncogene Medium 36418470
2013 CCL18 inhibits CCR1, CCR2, CCR4, and CCR5-mediated chemotaxis without binding to these receptors; instead, CCL18 selectively displaces heparin-bound chemokines from glycosaminoglycans (GAGs) on the endothelial surface, thereby functioning as a regulatory inhibitor of chemokine-mediated leukocyte recruitment. Schild plot analysis for competitive antagonism, binding assays to CCR-transfected cells, GAG displacement assays with heparin-bound chemokines PloS one Medium 23951310
2006 Adenoviral overexpression of CCL18 in mouse lungs induces massive perivascular and peribronchial T lymphocyte infiltration and T lymphocyte-dependent collagen accumulation; T cell depletion abrogates CCL18-induced collagen deposition; CCL18 prestimulation of T cells upregulates TGF-beta1, which drives collagen production in T lymphocyte/fibroblast cocultures. Adenoviral gene delivery in vivo, antilymphocyte serum depletion, immunohistochemistry, flow cytometry, ELISA, T lymphocyte/fibroblast coculture Arthritis and rheumatism Medium 16868995
2010 CCL18 attenuates CXCL12/CXCR4-mediated responses (calcium mobilization, chemotaxis, pseudo-emperipolesis, proliferation) in pre-B ALL cells by binding to GPR30; antibodies against GPR30 abolished CCL18 binding and its functional effects. Calcium flux assays, chemotaxis assays, GPR30-blocking antibodies, CCL18 binding to GPR30-expressing cells Journal of cellular physiology Medium 20568229
2003 CCL18 production by immature dendritic cells is selectively down-regulated during maturation (by LPS, TNF, CD40L, pathogens), whereas IL-10 and vitamin D3 strongly promote CCL18 secretion; CCL18 was found to be chemotactic for immature dendritic cells. Cytokine stimulation of monocyte-derived DCs, ELISA for CCL18, chemotaxis assays Journal of immunology Medium 12646652
2019 CCL18 promotes breast cancer metastasis via Annexin A2 as a downstream molecule of Nir1 (PITPNM3); CCL18 upregulates AnxA2 which promotes invasion and metastasis through the PI3K/Akt/GSK3β/Snail signaling pathway and F-actin polymerization via integrin β1. Western blot, siRNA knockdown of AnxA2, PI3K inhibitor LY294002, F-actin measurement, Matrigel invasion assay, spontaneous metastasis in SCID mice Oncology reports Medium 31894281
2015 CCL18 reduces miR98 and miR27b expression via the N-Ras/ERK/PI3K/NFκB/Lin28b signaling pathway, forming a positive feedback loop that sustains CCL18 signaling and promotes EMT and metastasis of breast cancer cells. miRNA expression profiling, pathway inhibitor studies, overexpression/knockdown of miR98 and miR27b, invasion/migration assays Oncotarget Medium 26244871
2018 CCL18 promotes bladder cancer cell invasion, migration, and EMT by binding to CCR8; blocking CCR8 with a small molecule inhibitor or shRNA knockdown reverses CCL18-induced decrease in E-cadherin and increase in MMP-2 and VEGF-C. CCR8 shRNA knockdown, CCR8 small molecule inhibitor, Western blotting, invasion/migration assays Molecular medicine reports Medium 30592282
2022 In glioma, CCR8 is identified as a functional receptor for CCL18; downstream signaling involves ACP5 (acid phosphatase 5), and CCL18 promotes glioma cell growth and invasion via the CCR8-ACP5 axis. Humanized brain slice model with iPSC-derived human microglia, CCR8 identification, in vivo GBM mouse model, functional invasion assays Cell reports Medium 35417708
2008 Thrombin stimulates CCL18 release from mature dendritic cells (LPS-matured, PAR1/PAR3-expressing) via Rho-dependent signaling; CCL18 release requires ERK1/2 and Rho kinase activation. PAR-activating peptides, ERK1/2 and Rho kinase pharmacological inhibitors, ELISA for CCL18, actin polymerization assays, immunofluorescence Journal of immunology Medium 18606675
2018 ACAP4 is acetylated by PCAF acetyltransferase at Lys311 in response to CCL18 stimulation; dynamic acetylation of ACAP4 is essential for CCL18-induced breast cancer cell migration and invasion by reducing ACAP4 lipid-binding activity to permit robust ARF6-ACAP4 plasma membrane cycling. Mass spectrometry, co-IP of ACAP4 with PCAF, acetylation-mimicking and non-acetylatable ACAP4 mutants, cell migration assays Journal of molecular cell biology Medium 30395269
2020 Ezrin is acetylated by PCAF acetyltransferase in breast cancer cells in response to CCL18 stimulation; acetylation at the mapped site reduces ezrin lipid-binding activity, prevents Thr567 phosphorylation, and drives ezrin unfolding, enabling dynamic plasma membrane-cytosol cycling essential for CCL18-induced cell migration and invasion. Mass spectrometry, co-IP of ezrin with PCAF, atomic force microscopy, phosphorylation/acetylation mutants, cell migration assays Journal of molecular cell biology Medium 31638145
2022 CCL18 activates the ARF6/Src/PI3K/Akt signaling pathway; CCL18 increases ARF6 expression and p-AMAP1 via suppression of miR-760 in high metastatic breast cancer cells; exosomal miR-760 secreted by CCL18-stimulated high-metastatic cells is taken up by low-metastatic cells and promotes ARF6-mediated Src/PI3K/Akt signaling and EMT. ARF6 knockdown, miR-760 mimic/inhibitor, exosome uptake assays, Western blotting, in vivo tumor growth/metastasis models Molecular therapy oncolytics Medium 35399607
1999 The PARC/CCL18 gene was generated by fusion of two MIP-1alpha/LD78alpha-like genes on chromosome 17q11.2, explaining its high sequence similarity to MIP-1alpha but distinct chemotactic activity (toward lymphocytes rather than monocytes) and lack of shared receptor with MIP-1alpha. BAC clone genomic analysis, dot-plot sequence comparison, exon/intron structure analysis Genomics Medium 10049593
2021 M2-TAMs induce EMT of ovarian cancer cells by releasing CCL18; CCL18 induces M-CSF transcription in OvCa cells through ZEB1, and M-CSF drives M2 polarization of macrophages, establishing a CCL18-ZEB1-M-CSF positive feedback loop between OvCa cells and TAMs in spheroids. 3D coculture, transwell coculture, RNA-sequencing, Western blot, qRT-PCR, ZEB1 knockdown, intraperitoneal mouse model Journal for immunotherapy of cancer Medium 34969774
2024 Lactate regulates CCL18 expression in macrophages via H3K18 lactylation; lactate-treated macrophages (acting through Gpr132) promote OV cell proliferation and migration, effects reversed by CCL18 silencing or anti-CCL18 antibody. ChIP-qPCR for H3K18 lactylation at CCL18 locus, luciferase reporter assay, Gpr132 siRNA knockdown, anti-CCL18 antibody, xenograft mouse model Acta biochimica et biophysica Sinica Medium 39010846

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer cell 531 21481794
2003 Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Blood 252 12969956
2005 Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes. Journal of leukocyte biology 216 15784687
2004 Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica. Antimicrobial agents and chemotherapy 205 15388468
1996 High-level fluoroquinolone resistance in Streptococcus pneumoniae requires mutations in parC and gyrA. Antimicrobial agents and chemotherapy 191 9124836
1996 Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli. Antimicrobial agents and chemotherapy 185 8834907
2002 Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. The Journal of biological chemistry 169 11978786
1999 Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli. Antimicrobial agents and chemotherapy 163 10103193
2013 Identification of human CCR8 as a CCL18 receptor. The Journal of experimental medicine 157 23999500
1997 Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii. The Journal of antimicrobial chemotherapy 145 9222045
1996 Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro. Antimicrobial agents and chemotherapy 143 8913454
2012 The chemokine CCL18 causes maturation of cultured monocytes to macrophages in the M2 spectrum. Immunology 117 22117697
2003 Unique regulation of CCL18 production by maturing dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 117 12646652
2005 CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells. Journal of immunology (Baltimore, Md. : 1950) 113 15661937
1996 Quinolone-resistant Neisseria gonorrhoeae: correlation of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV with antimicrobial susceptibility profiles. Antimicrobial agents and chemotherapy 107 8849219
2003 Mutations in gyrA and parC genes in nalidixic acid-resistant Escherichia coli strains from food products, humans and animals. The Journal of antimicrobial chemotherapy 106 12654733
1997 Partitioning of plasmid R1. The ParM protein exhibits ATPase activity and interacts with the centromere-like ParR-parC complex. Journal of molecular biology 105 9217256
1998 Role of mutation in the gyrA and parC genes of nalidixic-acid-resistant salmonella serotypes isolated from animals in the United Kingdom. The Journal of antimicrobial chemotherapy 102 9687102
2003 Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa. International journal of antimicrobial agents 99 12727072
2020 CCL18 in the Progression of Cancer. International journal of molecular sciences 87 33114763
2011 Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine 86 21216880
2018 Mutations in ParC and GyrA of moxifloxacin-resistant and susceptible Mycoplasma genitalium strains. PloS one 85 29883482
1996 Quinolone-resistant mutants of escherichia coli DNA topoisomerase IV parC gene. Antimicrobial agents and chemotherapy 78 8851598
2021 Detection of gyrA and parC Mutations and Prevalence of Plasmid-Mediated Quinolone Resistance Genes in Klebsiella pneumoniae. Infection and drug resistance 75 33603418
2014 CCL18 promotes epithelial-mesenchymal transition, invasion and migration of pancreatic cancer cells in pancreatic ductal adenocarcinoma. International journal of oncology 75 25502147
2000 Horizontal transfer of parC and gyrA in fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrobial agents and chemotherapy 75 10722479
2001 CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis. Journal of leukocyte biology 74 11590198
2015 Resistance Mutations in gyrA and parC are Common in Escherichia Communities of both Fluoroquinolone-Polluted and Uncontaminated Aquatic Environments. Frontiers in microbiology 72 26696975
2018 Development and Validation of a Novel Pediatric Appendicitis Risk Calculator (pARC). Pediatrics 64 29535251
2002 Mutations in gyrA, gyrB, parC, and parE in quinolone-resistant strains of Neisseria gonorrhoeae. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 62 12529019
2022 CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype. Oncogene 60 36418470
2004 Role of TolC and parC mutation in high-level fluoroquinolone resistance in Salmonella enterica serotype Typhimurium DT204. The Journal of antimicrobial chemotherapy 60 14985270
2016 CCL18 from ascites promotes ovarian cancer cell migration through proline-rich tyrosine kinase 2 signaling. Molecular cancer 57 27613122
2015 CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 57 26449829
2015 CCL18 from tumor-cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway. Molecular carcinogenesis 57 26457987
2007 Structural analysis of the ParR/parC plasmid partition complex. The EMBO journal 57 17898804
2009 Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis. Clinica chimica acta; international journal of clinical chemistry 56 19808030
2021 Tumor-associated macrophages induced spheroid formation by CCL18-ZEB1-M-CSF feedback loop to promote transcoelomic metastasis of ovarian cancer. Journal for immunotherapy of cancer 55 34969774
2006 CCL18-stimulated upregulation of collagen production in lung fibroblasts requires Sp1 signaling and basal Smad3 activity. Journal of cellular physiology 54 16021625
2019 CCL18-induced HOTAIR upregulation promotes malignant progression in esophageal squamous cell carcinoma through the miR-130a-5p-ZEB1 axis. Cancer letters 53 31207321
2007 Expression and regulation of CCL18 in synovial fluid neutrophils of patients with rheumatoid arthritis. Arthritis research & therapy 51 17875202
2018 CCL18 secreted from M2 macrophages promotes migration and invasion via the PI3K/Akt pathway in gallbladder cancer. Cellular oncology (Dordrecht, Netherlands) 50 30276551
2011 Cytoplasmic CUL9/PARC ubiquitin ligase is a tumor suppressor and promotes p53-dependent apoptosis. Cancer research 50 21487039
2011 Alterations of gyrA, gyrB, and parC and Activity of Efflux Pump in Fluoroquinolone-resistant Acinetobacter baumannii. Osong public health and research perspectives 50 24159468
2021 The immunosuppressive and pro-tumor functions of CCL18 at the tumor microenvironment. Cytokine & growth factor reviews 49 33863622
2018 Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck. Cancer cell international 47 30181713
2018 CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells. Molecular medicine reports 46 30592282
2016 CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway. Molecular carcinogenesis 45 26756176
2010 Attenuation of CXCR4 responses by CCL18 in acute lymphocytic leukemia B cells. Journal of cellular physiology 44 20568229
2020 CCL18-induced LINC00319 promotes proliferation and metastasis in oral squamous cell carcinoma via the miR-199a-5p/FZD4 axis. Cell death & disease 43 32948745
2019 CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2. Oncology reports 43 31894281
2015 CCL18-mediated down-regulation of miR98 and miR27b promotes breast cancer metastasis. Oncotarget 43 26244871
2014 Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis. Journal of cellular biochemistry 43 24142406
2011 Up-regulation of the chemokine CCL18 by macrophages is a potential immunomodulatory pathway in cutaneous T-cell lymphoma. The American journal of pathology 42 21741937
2006 Induction of prolonged infiltration of T lymphocytes and transient T lymphocyte-dependent collagen deposition in mouse lungs following adenoviral gene transfer of CCL18. Arthritis and rheumatism 41 16868995
2018 Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1. Journal of molecular medicine (Berlin, Germany) 40 30426155
2023 Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19. Nature communications 39 36774347
1998 Development of fluoroquinolone resistance and mutations involving GyrA and ParC proteins among Neisseria gonorrhoeae isolates in Japan. The Journal of urology 39 9598572
2022 Combination Therapy for Mycoplasma genitalium, and New Insights Into the Utility of parC Mutant Detection to Improve Cure. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 38 34984438
2018 CCL18 - Beyond chemotaxis. Cytokine 38 29402725
2018 Analysis of mutational patterns in quinolone resistance-determining regions of GyrA and ParC of clinical isolates. International journal of antimicrobial agents 38 30582984
2005 Mutations in the gyrA and parC genes in ciprofloxacin-resistant clinical isolates of Acinetobacter baumannii in Korea. Microbiology and immunology 38 16034208
2006 PKCalpha mediates CCL18-stimulated collagen production in pulmonary fibroblasts. American journal of respiratory cell and molecular biology 36 16601239
2015 Association between mutations in gyrA and parC genes of Acinetobacter baumannii clinical isolates and ciprofloxacin resistance. Iranian journal of basic medical sciences 35 26221488
2006 Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, toll-like receptors and rheumatoid synovial fluid. BMC immunology 35 16984635
1999 Chemokine PARC gene (SCYA18) generated by fusion of two MIP-1alpha/LD78alpha-like genes. Genomics 35 10049593
2024 Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer. Acta biochimica et biophysica Sinica 34 39010846
2020 Discovery of seven novel mutations of gyrB, parC and parE in Salmonella Typhi and Paratyphi strains from Jiangsu Province of China. Scientific reports 33 32355184
2013 The MukB-ParC interaction affects the intramolecular, not intermolecular, activities of topoisomerase IV. The Journal of biological chemistry 33 23349462
2018 Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy. Cancer chemotherapy and pharmacology 32 29728799
2016 YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia. Respirology (Carlton, Vic.) 32 27782361
2014 Fluoroquinolone resistance and molecular characterization of gyrA and parC quinolone resistance-determining regions in Escherichia coli isolated from poultry. Poultry science 32 24706962
2018 The long non-coding RNA CRNDE competed endogenously with miR-205 to promote proliferation and metastasis of melanoma cells by targeting CCL18. Cell cycle (Georgetown, Tex.) 31 30257602
2013 Role of CCL18 in asthma and lung immunity. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 31 23786278
2022 CCL18 promotes breast cancer progression by exosomal miR-760 activation of ARF6/Src/PI3K/Akt pathway. Molecular therapy oncolytics 30 35399607
2018 Surgical trauma-induced CCL18 promotes recruitment of regulatory T cells and colon cancer progression. Journal of cellular physiology 30 30216450
2022 Microglia/macrophage-derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model. Cell reports 29 35417708
2022 GyrB in silico mining in 27 151 global gonococcal genomes from 1928-2021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility. The Journal of antimicrobial chemotherapy 29 36308328
2020 MiR-484 suppressed proliferation, migration, invasion and induced apoptosis of gastric cancer via targeting CCL-18. International journal of experimental pathology 29 32985776
2008 CCL18 is expressed in patients with bullous pemphigoid and parallels disease course. The British journal of dermatology 29 19120345
2002 The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions. Biochemistry 29 12269820
2013 Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection. BMC urology 28 24011266
2002 Expression of the chemokine PARC mRNA in bronchoalveolar cells of patients with sarcoidosis. Immunology letters 28 12161279
2005 Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse development. Molecular and cellular biology 27 15964813
1996 Analysis of the promoter of the auxin-inducible gene, parC, of tobacco. Plant & cell physiology 27 8979393
2021 Histamine Increases Th2 Cytokine-Induced CCL18 Expression in Human M2 Macrophages. International journal of molecular sciences 26 34769080
2008 Mature dendritic cells express functional thrombin receptors triggering chemotaxis and CCL18/pulmonary and activation-regulated chemokine induction. Journal of immunology (Baltimore, Md. : 1950) 26 18606675
2000 Pseudoexons and regulatory elements in the genomic sequence of the beta-chemokine, alternative macrophage activation-associated CC-chemokine (AMAC)-1. Cytokine 26 10671296
2018 Acetylation of ACAP4 regulates CCL18-elicited breast cancer cell migration and invasion. Journal of molecular cell biology 24 30395269
2008 Mycobacterium tuberculosis induces CCL18 expression in human macrophages. Scandinavian journal of immunology 24 18959625
2004 Analysis of gyrA and parC mutations in enterococci from environmental samples with reduced susceptibility to ciprofloxacin. FEMS microbiology letters 24 14769469
2019 gyrA and parC mutations in fluoroquinolone-resistant Neisseria gonorrhoeae isolates from Kenya. BMC microbiology 22 30961546
2019 The identification of CCL18 as biomarker of disease activity in localized scleroderma. Journal of autoimmunity 22 31006523
2013 CCL18 exhibits a regulatory role through inhibition of receptor and glycosaminoglycan binding. PloS one 22 23951310
2005 Fluoroquinolone resistance and gyrA and parC mutations of Escherichia coli isolated from chicken. Journal of microbiology (Seoul, Korea) 22 16273029
2001 Molecular epidemiology and mutations at gyrA and parC genes of ciprofloxacin-resistant Escherichia coli isolates from a Taiwan medical center. Microbial drug resistance (Larchmont, N.Y.) 22 11310803
2020 Acetylation of ezrin regulates membrane-cytoskeleton interaction underlying CCL18-elicited cell migration. Journal of molecular cell biology 21 31638145
2019 Discovery of CCL18 antagonist blocking breast cancer metastasis. Clinical & experimental metastasis 21 31062206
2002 Mutation patterns in gyrA and parC genes of ciprofloxacin resistant isolates of Neisseria gonorrhoeae from India. Sexually transmitted infections 21 12473806
2017 Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: a prospective observational study. Journal of translational medicine 20 28222799