Affinage

CCL11

Eotaxin · UniProt P51671

Length
97 aa
Mass
10.7 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL11 (eotaxin-1) is a secreted CC chemokine that drives eosinophil and TH2-cell recruitment and tissue remodeling through the G protein-coupled receptor CCR3 (PMID:8676064, PMID:8642344, PMID:9302298, PMID:16210640). It binds CCR3 with sub-nanomolar affinity and selectively triggers calcium flux and chemotaxis in CCR3-expressing eosinophils and TH2 (but not TH1) cells (PMID:8676064, PMID:8642344, PMID:9302298); the receptor interaction is structurally governed by sulfotyrosine residues in the CCR3 N-terminus that form hydrophobic, salt-bridge, and cation-π contacts with conserved CCL11 residues, with receptor sulfation enhancing activity (PMID:25450766). Downstream of CCR3, CCL11 activates the ERK1/2 (p42/p44) MAPK pathway to drive actin polymerization and chemotaxis (PMID:10415066). Beyond CCR3, CCL11 acts as a CCR5 agonist and a partial agonist/antagonist at CCR2b, where it competitively displaces MCP-1 (PMID:11264152, PMID:11559700). CCL11 functions broadly across cell types beyond leukocytes: it induces CCR3-dependent migration of endothelial cells and angiogenesis (PMID:11390513), smooth muscle cell migration (PMID:15130922), fibroblast proliferation, collagen synthesis and profibrotic activity (PMID:16387592), osteoclast precursor migration and bone resorption (PMID:28706221), and microglial migration with NOX1-dependent reactive oxygen species production and excitotoxicity (PMID:26184677). In vivo, CCL11 acts redundantly with eotaxin-2 (CCL24) upstream of CCR3 to drive airway eosinophilia (PMID:16210640), contributes to bleomycin-induced lung fibrosis (PMID:16314464), and drives gastrointestinal and colonic eosinophilia through β7-integrin-dependent trafficking and macrophage/epithelial sources (PMID:11733500, PMID:18981162). CCL11 transcription is induced by TNF-α/IL-1β via NF-κB and by IL-4/IL-13 via STAT6 through distinct promoter elements (PMID:9120022, PMID:10586089, PMID:11254707), by IL-9 (PMID:15294996), by IL-17A via JAK2/ERK-driven STAT3 binding to the STAT6 site (PMID:19265112), by oncostatin M via ERK/p38 (PMID:12496442), and through Brg1/NF-κB cooperation (PMID:35614068); it is suppressed by ATX-LPA signaling acting on c-Jun (PMID:38195933). The active chemokine is inactivated by mast cell β-tryptase and chymase, which cleave CCL11 and abrogate its chemotactic activity (PMID:16517749).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Establishing the receptor for a newly described eosinophil chemoattractant answered how CCL11 achieves cell-type selectivity, identifying CCR3 as its high-affinity receptor on eosinophils.

    Evidence Radioligand binding and transwell chemotaxis in CCR3-transfected cells, plus Ca2+ flux pharmacology

    PMID:8642344 PMID:8676064

    Open questions at the time
    • Affinity/selectivity mapped pharmacologically but binding-site residues not defined
    • Downstream signaling cascade not yet resolved
  2. 1997 High

    Demonstrating CCR3 expression on TH2 (not TH1) cells extended CCL11's role beyond eosinophil recruitment to selective TH2 lymphocyte trafficking in allergy.

    Evidence Anti-CCR3 antibody subset isolation with Ca2+ and chemotaxis assays

    PMID:9302298

    Open questions at the time
    • In vivo TH2 recruitment contribution relative to eosinophils not quantified
  3. 1999 High

    Dissecting the eotaxin promoter resolved how distinct inflammatory inputs converge on CCL11, mapping TNF-α→NF-κB and IL-4→STAT6 to separate functional promoter elements.

    Evidence Promoter mutagenesis, luciferase reporter, and EMSA in BEAS-2B cells

    PMID:10586089

    Open questions at the time
    • Cell-type-specific weighting of the two elements not addressed
    • Other inducers not yet mapped
  4. 1999 High

    Placing ERK1/2 MAPK downstream of CCR3 and upstream of actin remodeling defined the intracellular signaling route linking receptor engagement to chemotaxis.

    Evidence MEK inhibitor (PD98059) with phosphorylation, intravital rolling, chemotaxis, and actin polymerization readouts

    PMID:10415066

    Open questions at the time
    • Gα subunit coupling not directly demonstrated in this study
    • Other parallel pathways (PI3K, PLC) not dissected
  5. 2001 High

    Profiling CCL11 across additional chemokine receptors revealed it is not CCR3-exclusive but a CCR5 agonist and CCR2b partial agonist/antagonist, broadening its receptor pharmacology and cross-regulatory potential.

    Evidence Binding, Ca2+ flux, internalization, and chemotaxis assays in monocytes and CCR2b/CCR5 transfectants

    PMID:11264152 PMID:11559700

    Open questions at the time
    • Physiological significance of CCR2/CCR5 engagement in vivo unclear
    • Structural basis of partial agonism not defined
  6. 2001 Medium

    Identifying angiogenic, endothelial, and β7-integrin-dependent gastrointestinal functions established that CCL11 acts directly on non-leukocyte targets and on eosinophil tissue homing beyond simple chemotaxis.

    Evidence Endothelial CAM/Matrigel/aortic-ring angiogenesis assays; transgenic overexpression, KO rescue, and integrin blockade in intestine

    PMID:11390513 PMID:11733500

    Open questions at the time
    • Angiogenesis findings single-lab
    • Signaling downstream of CCR3 in endothelium not dissected
  7. 2004 Medium

    Expanding the inducer repertoire to IL-9, and target cells to smooth muscle, showed CCL11 is a convergence node for multiple TH2/airway cytokines acting on structural cells.

    Evidence Promoter reporter, actinomycin D chase, neutralizing antibodies (IL-9), and CCR3-blocked SMC chemotaxis

    PMID:15130922 PMID:15294996

    Open questions at the time
    • IL-9 signaling intermediates to the promoter not fully mapped
    • SMC migration consequence in vivo not tested
  8. 2005 High

    Genetic epistasis and tissue-specific studies established CCL11 as functionally redundant with CCL24 upstream of CCR3 in airway eosinophilia and as a direct profibrotic and neuro-targeting effector.

    Evidence Eotaxin-1/2/CCR3 KO genotypes in OVA model; bleomycin fibrosis KO/overexpression; CCR3-blocked fibroblast assays and airway-nerve studies

    PMID:16210640 PMID:16314464 PMID:16374515 PMID:16387592

    Open questions at the time
    • Mechanism of profibrotic signaling beyond CCR3 engagement not resolved
    • Neuronal CCL11 source vs leukocyte source contributions not separated
  9. 2006 High

    Identifying mast cell β-tryptase and chymase as CCL11-inactivating proteases defined a post-secretion control point limiting eosinophil chemotactic activity.

    Evidence Purified protease cleavage with ELISA immunoreactivity, chemotaxis, and inhibitor controls

    PMID:16517749

    Open questions at the time
    • Cleavage sites not mapped
    • In vivo relevance of protease inactivation not demonstrated
  10. 2009 High

    Mapping the IL-17A→JAK2/ERK→STAT3 axis onto the CCL11 promoter showed that a TH17 cytokine co-opts the STAT6 consensus site, integrating CCL11 into non-TH2 inflammation.

    Evidence ChIP, dominant-negative STAT3, siRNA knockdown, and JAK2/ERK inhibitors in airway smooth muscle cells

    PMID:19265112

    Open questions at the time
    • Cross-talk between STAT3 and STAT6 occupancy not resolved
    • In vivo IL-17A dependence not tested here
  11. 2013 Medium

    Defining myeloid NF-κB (RelA/p65) and Brg1/NF-κB requirements clarified cell-type-specific and chromatin-level control of CCL11 in colitis and liver regeneration.

    Evidence Myeloid-specific p65 KO in DSS colitis; ChIP and liver-specific Brg1 KO with adenoviral CCL11 rescue

    PMID:23562811 PMID:25450766 PMID:35614068

    Open questions at the time
    • Relationship between Brg1 and the canonical promoter elements not fully integrated
    • STAT6-independence of macrophage response context-specific
  12. 2014 High

    Structural determination of the CCL11–CCR3 N-terminal sulfopeptide complex provided the atomic basis for receptor recognition and showed sulfotyrosine modification governs binding.

    Evidence NMR/structural determination with tyrosine-sulfation mutagenesis and functional receptor assays

    PMID:25450766

    Open questions at the time
    • Structure of intact full-length receptor-ligand complex not solved
    • Conformational changes driving G protein activation not captured
  13. 2024 Medium

    Discovering ATX-LPA→c-Jun suppression of CCL11 identified a negative regulatory loop linking CCL11/eosinophils to tumor microenvironment control.

    Evidence Genetic/pharmacologic ATX inhibition with c-Jun activity, promoter analysis, and intratumor eosinophil/apoptosis quantification in PDAC

    PMID:38195933

    Open questions at the time
    • Direct c-Jun binding to the CCL11 promoter not fully mapped
    • Single-lab finding in one tumor context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse CCL11-responsive non-leukocyte cell types (osteoclasts, microglia, trophoblasts, chondrocytes) integrate CCR3 signaling into distinct functional outputs, and the physiological role of CCR2/CCR5 engagement, remain unresolved.
  • Cell-type-specific downstream signaling logic undefined
  • In vivo significance of non-CCR3 receptor usage unestablished
  • Trophoblast and chondrocyte effects lack receptor-blocking validation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 2
Partners
CCR2CCR3CCR5

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CCL11 (eotaxin) binds with high affinity to the G protein-coupled receptor CKR-3 (CCR3), which is selectively expressed on eosinophils. Cells transfected with CKR-3 cDNA specifically bound radiolabeled CCL11 and migrated in chemotaxis assays toward CCL11, RANTES, and MCP-3, but not other chemokines, establishing CCR3 as the primary CCL11 receptor on eosinophils. Radioligand binding assays, cDNA transfection, transwell chemotaxis assays, Northern blot, monoclonal antibody staining The Journal of experimental medicine High 8642344 8676064
1996 CCR3 expressed on eosinophils binds CCL11 with Kd ~0.1 nM, RANTES with Kd ~3.1 nM, and MCP-3 with Kd ~2.7 nM, and triggers intracellular Ca2+ flux in response to CCL11, RANTES, and MCP-3, but not MIP-1α or MIP-1β, indicating ligand selectivity and G protein-coupled signaling. Stable transfection in AML14.3D10 cells, competition binding, Ca2+ flux assay The Journal of experimental medicine High 8642344
1997 CCR3 is expressed by human TH2 (but not TH1) cells; CCL11 stimulates intracellular calcium increases and chemotaxis specifically in CCR3+ T cells, providing a mechanism for selective TH2 cell recruitment in allergic reactions. Anti-CCR3 antibody isolation of T cell subsets, intracellular Ca2+ measurement, chemotaxis assay Science High 9302298
1997 TNF-α and IL-1β induce CCL11 mRNA accumulation in pulmonary epithelial cell lines (A549, BEAS-2B) in a dose-dependent manner; IFN-γ enhances this induction; dexamethasone suppresses cytokine-induced CCL11 mRNA and protein secretion; cycloheximide augments induction, suggesting a labile repressor protein. These cytokine-induced increases correlate with increased CCL11 protein secretion. RT-PCR, ELISA, cycloheximide/dexamethasone pharmacologic manipulation of cultured cell lines The Journal of clinical investigation Medium 9120022
1999 CCL11 gene transcription is activated by NF-κB (in response to TNF-α) and STAT6 (in response to IL-4) through distinct binding sites in the eotaxin promoter. Mutation of the NF-κB site abolished TNF-α-driven activation; mutation of the STAT6 site abolished IL-4-driven activation; double mutation abolished all transcriptional activation. EMSA confirmed factor binding to the respective promoter elements. Luciferase reporter assays with promoter deletion/mutation constructs, EMSA, transfection in BEAS-2B cells Journal of immunology High 10586089
1999 CCL11-induced eosinophil migration requires activation of the p42/p44 MAPK (ERK1/2) pathway. The MEK inhibitor PD98059 dramatically reduced eotaxin-induced eosinophil rolling in vivo and chemotaxis in vitro, and inhibited actin polymerization/rearrangement, placing MAPK activation downstream of CCR3 signaling and upstream of cytoskeletal remodeling during chemotaxis. In vitro phosphorylation assay, MEK inhibitor (PD98059), intravital microscopy, transwell chemotaxis, actin polymerization assay Journal of immunology High 10415066
2001 CCL11 is a CCR5 agonist and a CCR2 antagonist. CCL11 at 100 nM triggered CCR5 (Ca2+ flux, receptor internalization) but did not activate CCR2 even at 1 µM, while competitively displacing MCP-1 from CCR2 and inhibiting MCP-1-induced chemotaxis and enzyme release. CCL11 induced CCR5 internalization in human monocytes and transfected cells. Calcium flux assay, receptor internalization assay, 125I-MCP-1 competition binding, chemotaxis assay in human monocytes and transfected cells Blood High 11264152
2001 CCL11 is a partial agonist of CCR2b. At 1 µM, CCL11 recruited CCR2b-transfected cells in chemotaxis, while sub-stimulatory concentrations inhibited MCP-1-induced chemotaxis and Ca2+ flux via CCR2b. Radiolabeled CCL11 bound CCR2b with Kd ~7.5 nM (vs. ~1.68 nM at CCR3). CCR2-specific (not CCR3-specific) antagonism blocked this CCL11-mediated migration. Radioligand binding, Ca2+ flux assay, chemotaxis assay with CCR2b/CCR3 transfectants and THP-1 cells The Journal of biological chemistry High 11559700
2001 CCL11 induces chemotaxis and in vivo angiogenesis via CCR3 expressed on human microvascular endothelial cells. The chemotactic response was inhibited by antibodies to either CCL11 or CCR3. CCL11 induced blood vessel formation in chick chorioallantoic membrane and Matrigel plug assays; rat aortic ring sprouting assay showed angiogenesis is direct and not mediated by eosinophil products. Chemotaxis assay, antibody neutralization, CAM assay, Matrigel plug assay, rat aortic ring sprouting assay, flow cytometry for CCR3 Journal of immunology Medium 11390513
2001 TNF-α-induced CCL11 expression in fibroblasts is mediated through STAT6, not solely NF-κB. TNF-α activated the CCL11 promoter via an NF-κB/STAT6 composite element, and this required STAT6 DNA binding; promoter constructs with mutated STAT6 sites were unresponsive to TNF-α. A trans-dominant negative STAT6 protein inhibited TNF-α-induced CCL11 secretion in primary fibroblasts. Luciferase promoter reporter in STAT6-deficient HEK293 cells with STAT6 cotransfection, dominant-negative STAT6 overexpression, ELISA Journal of immunology High 11254707
2004 CCL11 induces CCR3-dependent smooth muscle cell (SMC) migration. CCR3 mRNA and protein are expressed in mouse aortic SMCs; CCL11 induced concentration-dependent SMC chemotaxis in Boyden chamber and scrape-wound assays that were blocked by anti-CCR3 (but not anti-CCR2) antibody. CCL11 had no effect on SMC proliferation. RT-PCR, Western blot, flow cytometry, Boyden chamber chemotaxis, scrape-wound assay, antibody neutralization Arteriosclerosis, thrombosis, and vascular biology Medium 15130922
2005 CCL11 signaling via CCR3 mediates eosinophil recruitment specifically to airway nerves (not just to lung tissue broadly) in antigen-challenged guinea pigs. A CCR3 antagonist prevented clustering of eosinophils around nerves and preserved M2 muscarinic receptor function, blocking vagal hyperreactivity. CCL11 protein was detected in airway parasympathetic neurons; IL-4 and IL-13 increased CCL11 expression in cultured airway neurons and human neuroblastoma cells. In vivo CCR3 antagonist treatment, immunostaining of airway nerves, M2R functional assay (vagal stimulation), cultured guinea pig and human airway neurons The Journal of clinical investigation Medium 16374515
2005 CCL11 and CCR3 are required for pulmonary granulocyte recruitment and development of bleomycin-induced lung fibrosis. CCL11-deficient mice developed significantly reduced fibrosis and lower TGF-β1 expression; overexpression of CCL11 enhanced fibrosis. Neutralizing CCR3 antibodies reduced fibrosis, eosinophilia, neutrophilia, and profibrotic cytokines. CCL11 knockout mice, CCL11 overexpression, anti-CCR3 antibody neutralization, histology, cytokine measurement The American journal of pathology Medium 16314464
2005 CCL11 directly activates mouse eosinophil secretion of enzymatically active RNases (EARs) by piecemeal degranulation (EC50 ~5 nM), via CCR3 on both intact eosinophils and cell-free eosinophil granules. Cell-free granules expressing functional CCR3 secreted EAR and eosinophil peroxidase in response to CCL11. In vitro RNase activity assay, ultrastructural electron microscopy (piecemeal degranulation), CCR3-expressing cell-free granule stimulation FASEB journal Medium 22294786
2006 Mast cell β-tryptase selectively cleaves CCL11 (eotaxin) and RANTES, abrogating their eosinophil chemotactic activities. The proteolytic activity of tryptase (requiring heparin) was necessary; heat inactivation and leupeptin reversed the effect. Mast cell chymase also reduced CCL11 immunoreactivity but did not affect RANTES. Neither enzyme affected other tested chemokines/cytokines. Purified β-tryptase incubation with recombinant and cell-derived CCL11/RANTES, ELISA immunoreactivity, chemotaxis assay with tryptase-pretreated chemokines, protease inhibitor and heat-inactivation controls Journal of immunology High 16517749
2004 IL-9 induces CCL11 expression in human airway smooth muscle (ASM) cells via transcriptional activation of the CCL11 promoter. IL-9Rα is expressed on ASM cells; neutralizing anti-IL-9 (but not anti-IL-4 or anti-IL-13) antibodies significantly reduced IL-9-induced CCL11 production. Actinomycin D blocked IL-9-induced CCL11 mRNA and protein, confirming transcriptional regulation. Conditioned medium from IL-9-stimulated ASM cells attracted eosinophils. ELISA, real-time RT-PCR, luciferase promoter reporter transfection, neutralizing antibody blockade, actinomycin D chase, chemotaxis assay Journal of immunology High 15294996
2009 IL-17A induces CCL11 expression in human airway smooth muscle cells via STAT3 phosphorylation (not STAT6 or STAT5). STAT3 binds the STAT6 consensus site in the CCL11 promoter upon IL-17A stimulation; dominant-negative STAT3β abolishes IL-17A-induced CCL11 promoter activity; STAT3 siRNA knockdown reduces CCL11 mRNA and protein. IL-17A-induced STAT3 phosphorylation is sensitive to JAK2 and ERK1/2 inhibitors. Promoter reporter assay, EMSA/ChIP (in vivo binding), dominant-negative and siRNA knockdown of STAT3, JAK2/ERK inhibitors, ELISA, RT-PCR Journal of immunology High 19265112
2005 Eotaxin-1 and eotaxin-2 act synergistically to recruit eosinophils to the lung in an OVA asthma model via CCR3. Individual deletion of eotaxin-1 or eotaxin-2 had modest effects on tissue eosinophilia, but eotaxin-1/2 double-knockout mice showed a marked decrease approaching the level seen in CCR3-deficient mice, establishing epistasis: CCL11 and CCL24 act redundantly upstream of CCR3 to drive peribronchial/perivascular eosinophil accumulation. Targeted gene deletion (eotaxin-1 KO, eotaxin-2 KO, DKO, CCR3 KO), OVA allergy model, BAL and tissue eosinophil counts, histology Journal of immunology High 16210640
2014 Crystal/NMR structure of CCL11 bound to sulfotyrosine-containing N-terminal peptide of CCR3 (residues 8–23, with two sulfotyrosine residues): sulfotyrosines make hydrophobic, salt bridge and cation-π interactions with conserved CC chemokine residues. Intact CCR3 is sulfated, and sulfation enhances receptor activity. The CCR3 N-terminus orients differently relative to CCL11 than CXC chemokine receptor N-termini do relative to their ligands. NMR/structural determination of CCL11-CCR3 peptide complex, tyrosine sulfation mutagenesis, functional receptor activity assays Structure High 25450766
2005 CCL11 (eotaxin-1) has a direct profibrogenic effect on human lung fibroblasts via CCR3. CCR3 is constitutively expressed on lung/bronchial fibroblasts. CCL11 increased fibroblast proliferation, MMP-2 activity, collagen synthesis, and migration; enhanced migration was completely blocked by anti-CCR3 neutralizing antibodies. CCL11 did not induce myofibroblast differentiation, contractility, or TGF-β1 release. Flow cytometry, RT-PCR, Northern blot, Boyden chamber migration, thymidine/proline incorporation, gelatin zymography, ELISA, anti-CCR3 neutralization The Journal of allergy and clinical immunology Medium 16387592
2015 CCL11 released from activated astrocytes is taken up by microglia expressing CCR3; CCL11 promotes microglial migration and induces microglial production of reactive oxygen species by upregulating NADPH oxidase 1 (NOX1), thereby enhancing excitotoxic neuronal death. These effects were reversed by NOX1 inhibition. Primary astrocyte/microglia cultures, CCL11 neutralization/addition, ROS measurement, NOX1 inhibitor, migration assay, neuronal toxicity assay Glia Medium 26184677
2001 Intestinal enterocyte-derived CCL11 drives gastrointestinal eosinophilia via a β7-integrin-dependent mechanism. Transgenic mice overexpressing eotaxin in intestinal epithelium (via FABPI promoter) showed significantly elevated lamina propria eosinophil counts; eotaxin-induced intestinal eosinophilia was substantially higher than IL-5-induced eosinophilia; genetic rescue of CCL11-deficient mice by eotaxin transgene restored gastrointestinal eosinophil levels; β7 integrin blockade abrogated eotaxin-induced intestinal eosinophilia. Transgenic mouse overexpression, eotaxin KO rescue experiments, β7 integrin knockout/blockade, intestinal eosinophil quantification The Journal of biological chemistry High 11733500
2007 TLR3 signaling via an intracellular (endosomal) pool mediates dsRNA-induced CCL11 synthesis in bronchial smooth muscle cells. Poly(I:C) induced CCL11 and RANTES production; TLR3-specific siRNA knockdown and bafilomycin A1 (endosomal acidification inhibitor) prominently inhibited CCL11 synthesis; surface anti-TLR3 antibody did not block poly(I:C)-induced CCL11, and TLR3 co-localized intracellularly with poly(I:C). IL-4 synergistically increased poly(I:C)-induced CCL11, and eosinophil chemotaxis driven by conditioned medium was mostly blocked by anti-CCL11 antibody. TLR3 siRNA knockdown, bafilomycin A1 inhibition, confocal microscopy (TLR3/poly(I:C) co-localization), anti-TLR3 surface blockade, chemotaxis assay with neutralizing antibody Journal of immunology High 17182588
2012 TGF-β1 synergizes with IL-13 to increase CCL11 expression in human airway fibroblasts via STAT6. TGF-β1 activates MEK/ERK to reduce IL-13Rα2 expression, overcoming IL-13's negative autoregulatory feedback on its own receptor, thereby augmenting STAT6 phosphorylation, nuclear translocation, and binding to the CCL11 promoter. STAT6 siRNA knockdown abolished both STAT6 activity and CCL11 expression. Transcriptional (nuclear run-on) and posttranscriptional (mRNA stability) assays confirmed transcriptional control is dominant. Nuclear run-on, mRNA stability assay, STAT6 siRNA knockdown, MEK/ERK inhibitors, STAT6 ChIP, ELISA Journal of immunology High 22573806
2013 Myeloid cell-specific NF-κB (RelA/p65) is required for CCL11 expression and eosinophilic inflammation in experimental colitis. RelA/p65-deficient myeloid cells showed attenuated Ccl11 expression and eosinophil recruitment in DSS colitis. In vitro, calprotectin (S100a8/S100a9) induced CCL11 production from macrophages in a p65-dependent manner. STAT-6 was not required for the macrophage CCL11 response. Myeloid-specific p65 KO mice (RelA/p65Δmye), DSS colitis model, STAT6 KO comparison, bone marrow-derived macrophage stimulation, gene array Journal of immunology Medium 23562811
2011 CCL11 (eotaxin-1) expression in hepatocytes is trans-activated by the chromatin remodeling factor Brg1 in cooperation with NF-κB/RelA. Brg1 directly binds the proximal eotaxin promoter and activates transcription. NF-κB knockdown or inhibition blocked Brg1 recruitment to the promoter and prevented eotaxin induction. Liver-specific Brg1 deletion attenuated eosinophil infiltration and eotaxin expression; adenoviral CCL11 overexpression rescued the delayed liver regeneration caused by Brg1 deficiency. ChIP (Brg1 binding to eotaxin promoter), liver-specific Brg1 KO, adenoviral CCL11 overexpression/RNAi rescue, NF-κB inhibition, ELISA, qPCR Cell death & disease Medium 35614068
2024 ATX-LPA signaling suppresses CCL11 expression via an autocrine feedback loop in which LPA negatively regulates the AP-1 transcription factor c-Jun, which in turn suppresses CCL11 transcription, thereby reducing eosinophil accumulation in the pancreatic ductal adenocarcinoma microenvironment. Genetic or pharmacologic ATX inhibition increased intratumor CCL11, eosinophil numbers, and tumor cell apoptosis. Genetic ATX knockout, pharmacologic ATX inhibition, c-Jun activity assays, CCL11 promoter analysis, intratumor eosinophil quantification, tumor progression measurement Nature cancer Medium 38195933
2011 IL-33 induces CCL11 (eotaxin-1) production in mouse lung fibroblasts; IL-33 and IL-13 synergistically induce CCL11 expression, as demonstrated by cytokine treatment of primary murine lung fibroblasts and the OVA asthma model. Primary murine lung fibroblast culture, cytokine stimulation, qPCR, ELISA, OVA mouse model International archives of allergy and immunology Low 21646790
2003 Oncostatin M (OSM) induces CCL11 production and mRNA expression in fibroblasts via ERK1/2 and p38 MAPK pathways (not STAT3 alone). STAT3 was activated by OSM, LIF, IL-6, and CT-1, but only OSM induced eotaxin; MEK inhibitor (PD98059) and p38 inhibitor (SB203580) partially reduced OSM-induced CCL11, indicating partial dependence on MAPK signaling. In vivo OSM overexpression caused eosinophil infiltration with elevated CCL11 mRNA. NIH 3T3/mouse lung fibroblast cultures, cytokine stimulation, MAPK inhibitors, STAT3 phosphorylation assay, adenovirus-mediated OSM overexpression in mice Journal of immunology Medium 12496442
2009 CCL11 stimulates proliferation and migration/invasion of ovarian carcinoma cell lines via CCR2, CCR3, and CCR5 (all three expressed on ovarian tumors). Neutralizing antibodies against each receptor inhibited these effects. CCL11-mediated proliferative effects were associated with activation of ERK1/2, MEK1, and STAT3 phosphorylation and increased production of cytokines and angiogenic factors. Neutralizing antibodies against CCR2, CCR3, CCR5, proliferation/invasion assays, phosphoprotein analysis (ERK1/2, MEK1, STAT3), multiplex cytokine assay Clinical cancer research Medium 19351767
2011 CCL11 induces MMP-3 mRNA expression in human chondrocytes in a dose-dependent manner via G protein-coupled receptor (eotaxin-1/CCR3) signaling. ERK and p38 MAPK inhibitors suppressed CCL11-induced MMP-3 expression, while PKA inhibitors enhanced it. MMP-3 protein secretion was regulated by the PLC-PKC cascade and JNK/MAPK pathways. Most MMP-3 was detected in conditioned media, not cell lysates, indicating active secretion. Dose-response MMP-3 mRNA/protein assay in SW1353 and primary chondrocytes, ERK/p38/PKA/PLC/PKC/JNK inhibitors, ELISA Journal of biomedical science Medium 22114952
2017 CCL11/CCR3 signaling stimulates osteoclast precursor migration and enhances bone resorption. Osteoblasts express CCL11 (increased under inflammatory conditions), while CCR3 is upregulated during osteoclast differentiation and co-localizes with CCL11. Exogenous CCL11 was internalized by osteoclasts and stimulated pre-osteoclast migration and bone resorption. In vivo inflammatory bone lesion model, primary osteoblast/osteoclast cultures, CCR3 immunostaining/co-localization, CCL11 internalization assay, migration assay, bone resorption assay Scientific reports Medium 28706221
2013 CCL11, CCL24, and CCL26 stimulate migration, invasion, and collagen IV/fibronectin adhesion of extravillous trophoblast (EVT) cells. All three eotaxins significantly increased MMP-2 activity without affecting TIMP-2 activity or cell number. This identifies a direct regulatory role for CCL11 in EVT functions critical for uterine spiral arteriole remodeling. xCELLigence real-time migration assay, wound-healing assay, Matrigel invasion assay, zymography, adhesion assay with extracellular matrix proteins Human reproduction Low 23477905
1997 The human eotaxin (CCL11) gene is located on chromosome 17q21.1-q21.2 (by FISH) and contains regulatory elements in its 5' flanking region conserved between human and mouse, including NF-κB, IFN-γ response element, and glucocorticoid response element sites, consistent with observed cytokine and glucocorticoid regulation of gene expression. Fluorescence in situ hybridization (FISH) chromosomal localization, genomic sequencing, cross-species promoter alignment Genomics Medium 9169149
2008 Intestinal macrophage- and epithelial-cell-derived CCL11 is the primary driver of colonic eosinophil recruitment in pediatric ulcerative colitis and DSS colitis. In DSS-treated eotaxin-2-/- mice, eosinophil recruitment was still intact, whereas eotaxin-1/2-/- mice showed CCL11-dependent eosinophil recruitment. CCL11 expression was restricted to F4/80+CD11b+ intestinal macrophages (DSS model) and CD68+ macrophages plus basolateral intestinal epithelial cells (UC). Eosinophil-deficient mice confirmed an effector role for eosinophils in DSS disease pathology. Gene array, qPCR, DSS colitis in eotaxin-1/2 KO and eosinophil-deficient mice, immunofluorescence cell-type identification Journal of immunology Medium 18981162
2006 Rosmarinic acid inhibits CCL11 and CCR3 expression in human dermal fibroblasts by suppressing IKK-β activity, thereby preventing IκBα phosphorylation/degradation and NF-κB nuclear translocation and DNA binding in response to TNF-α. ELISA, Western blot, NF-κB luciferase reporter, IKK-β activity assay, immunofluorescence (NF-κB nuclear translocation) British journal of pharmacology Medium 16604092

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science (New York, N.Y.) 818 9302298
1996 Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. The Journal of experimental medicine 493 8676064
1996 Cloning, expression, and characterization of the human eosinophil eotaxin receptor. The Journal of experimental medicine 441 8642344
1997 Expression of eotaxin by human lung epithelial cells: induction by cytokines and inhibition by glucocorticoids. The Journal of clinical investigation 310 9120022
1999 The MCP/eotaxin subfamily of CC chemokines. Cytokine & growth factor reviews 290 10379912
2012 Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut 277 22580413
2001 Eotaxin (CCL11) induces in vivo angiogenic responses by human CCR3+ endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 208 11390513
2005 The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. Journal of immunology (Baltimore, Md. : 1950) 190 16210640
1999 Activation of eotaxin gene transcription by NF-kappa B and STAT6 in human airway epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 187 10586089
1995 Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. The Journal of experimental medicine 184 7869037
2001 Eotaxin and the attraction of eosinophils to the asthmatic lung. Respiratory research 167 11686879
1999 Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth muscle cells. American journal of respiratory and critical care medicine 155 10351942
1999 Enhanced expression of eotaxin and CCR3 in atopic dermatitis. The Journal of investigative dermatology 154 10417617
2001 Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5. Blood 150 11264152
2008 Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis. Journal of immunology (Baltimore, Md. : 1950) 137 18981162
2015 CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia. Glia 129 26184677
1999 Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration. Journal of immunology (Baltimore, Md. : 1950) 120 10415066
1997 Role of the monocyte chemoattractant protein and eotaxin subfamily of chemokines in allergic inflammation. Journal of leukocyte biology 115 9365117
2003 Tear and mucus eotaxin-1 and eotaxin-2 in allergic keratoconjunctivitis. Ophthalmology 114 12623809
2005 Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. The Journal of clinical investigation 110 16374515
1997 Eotaxin expression and eosinophilic inflammation in asthma. Biochemical and biophysical research communications 109 9240429
2003 Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells. Cellular immunology 107 14698143
2007 Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Human pathology 102 17900656
2005 Role of Eotaxin-1 (CCL11) and CC chemokine receptor 3 (CCR3) in bleomycin-induced lung injury and fibrosis. The American journal of pathology 97 16314464
2001 STAT6 mediates eotaxin-1 expression in IL-4 or TNF-alpha-induced fibroblasts. Journal of immunology (Baltimore, Md. : 1950) 97 11254707
1999 Eotaxin and monocyte chemotactic protein-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals. The Journal of allergy and clinical immunology 97 10069883
2001 Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 94 11467997
2001 Eotaxin and asthma. Current opinion in pharmacology 92 11712747
2009 Role of eotaxin-1 signaling in ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 84 19351767
2012 Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset. Thorax 83 23015684
2005 The CC chemokine eotaxin/CCL11 has a selective profibrogenic effect on human lung fibroblasts. The Journal of allergy and clinical immunology 83 16387592
2000 Synergistic induction of eotaxin expression in human keratocytes by TNF-alpha and IL-4 or IL-13. Investigative ophthalmology & visual science 82 10798661
2005 Eotaxin-2 and eotaxin-3 expression is associated with persistent eosinophilic bronchial inflammation in patients with asthma after allergen challenge. The Journal of allergy and clinical immunology 81 15805998
2020 CCL-11 or Eotaxin-1: An Immune Marker for Ageing and Accelerated Ageing in Neuro-Psychiatric Disorders. Pharmaceuticals (Basel, Switzerland) 79 32887304
2015 CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjögren's Syndrome. Arthritis & rheumatology (Hoboken, N.J.) 77 26359802
2004 CCL11 (Eotaxin) induces CCR3-dependent smooth muscle cell migration. Arteriosclerosis, thrombosis, and vascular biology 74 15130922
2012 Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. The American journal of gastroenterology 73 22777338
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2001 Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. The Journal of biological chemistry 70 11733500
2002 Functional expression of the eotaxin receptor CCR3 in CD30+ cutaneous T-cell lymphoma. Blood 69 12393570
2011 Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study. Rheumatology (Oxford, England) 67 21266446
2007 Increased serum levels of CCL11/eotaxin in schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry 67 18096286
2002 Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils. The Journal of biological chemistry 67 11980903
2014 CCL11 as a potential diagnostic marker for asthma? The Journal of asthma : official journal of the Association for the Care of Asthma 66 24796647
2014 Structural basis of receptor sulfotyrosine recognition by a CC chemokine: the N-terminal region of CCR3 bound to CCL11/eotaxin-1. Structure (London, England : 1993) 66 25450766
2000 Expression of the chemokine eotaxin and its receptor, CCR3, in human endometrium. Biology of reproduction 65 10642580
2014 From airway inflammation to inflammatory bowel disease: eotaxin-1, a key regulator of intestinal inflammation. Clinical immunology (Orlando, Fla.) 64 24786916
2004 IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells. Journal of immunology (Baltimore, Md. : 1950) 64 15294996
2009 Critical role for STAT3 in IL-17A-mediated CCL11 expression in human airway smooth muscle cells. Journal of immunology (Baltimore, Md. : 1950) 63 19265112
2001 The CC chemokine eotaxin (CCL11) is a partial agonist of CC chemokine receptor 2b. The Journal of biological chemistry 61 11559700
2002 Regulation of human eotaxin-3/CCL26 expression: modulation by cytokines and glucocorticoids. Cytokine 59 12061839
2000 Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis. The Journal of clinical endocrinology and metabolism 58 10902814
2006 Mast cell beta-tryptase selectively cleaves eotaxin and RANTES and abrogates their eosinophil chemotactic activities. Journal of immunology (Baltimore, Md. : 1950) 56 16517749
2016 An Overlook to the Characteristics and Roles Played by Eotaxin Network in the Pathophysiology of Food Allergies: Allergic Asthma and Atopic Dermatitis. Inflammation 55 26861136
2007 Eotaxin-2 and colorectal cancer: a potential target for immune therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 54 17908961
2000 NMR solution structure and receptor peptide binding of the CC chemokine eotaxin-2. Biochemistry 54 10913244
2006 Rosmarinic acid as a downstream inhibitor of IKK-beta in TNF-alpha-induced upregulation of CCL11 and CCR3. British journal of pharmacology 53 16604092
2003 Oncostatin M regulates eotaxin expression in fibroblasts and eosinophilic inflammation in C57BL/6 mice. Journal of immunology (Baltimore, Md. : 1950) 53 12496442
2002 Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 52 12218106
2012 CCL11 (eotaxin-1): a new diagnostic serum marker for prostate cancer. The Prostate 51 23059958
2010 Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 51 20143648
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2005 Role of CCL11 in eosinophilic lung disease during respiratory syncytial virus infection. Journal of virology 49 15681407
2003 Eotaxin expression in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia. Oral diseases 49 14629326
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2011 Expression and effects of IL-33 and ST2 in allergic bronchial asthma: IL-33 induces eotaxin production in lung fibroblasts. International archives of allergy and immunology 48 21646790
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2021 CCL11 exacerbates colitis and inflammation-associated colon tumorigenesis. Oncogene 47 34625710
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2012 Expression of Ccl11 associates with immune response modulation and protection against neuroinflammation in rats. PloS one 46 22815714
2011 Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid. Clinical and experimental immunology 46 21985360
2012 CCL11 elicits secretion of RNases from mouse eosinophils and their cell-free granules. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 44 22294786
2001 Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease. Journal of hepatology 44 11394653
2009 Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 43 20030665
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2007 TLR3-mediated synthesis and release of eotaxin-1/CCL11 from human bronchial smooth muscle cells stimulated with double-stranded RNA. Journal of immunology (Baltimore, Md. : 1950) 42 17182588
2002 Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis. Allergy 42 11991282
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2010 Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis. Cytokine 41 20236835
2004 Threonine for alanine substitution in the eotaxin (CCL11) gene and the risk of incident myocardial infarction. Atherosclerosis 41 15186951
2003 Regulation of eosinophil migration and Th2 cell function by IL-5 and eotaxin. Current drug targets. Inflammation and allergy 41 14561170
2002 Increased expression of eotaxin and its specific receptor CCR3 in bullous pemphigoid. European journal of dermatology : EJD 41 11809592
2013 CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis. Journal of leukocyte biology 40 23904440
2005 Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. The British journal of dermatology 38 15948978
2001 Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and children. Allergy 38 11576081
2014 Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response. Cancer research 37 25336190
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2011 IκBα glutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES. The European respiratory journal 36 21719482
2003 RANTES, eotaxin and eotaxin-2 expression and production in patients with aspirin triad. Allergy 36 14616128
2002 Regulatory effects of eotaxin, eotaxin-2, and eotaxin-3 on eosinophil degranulation and superoxide anion generation. Experimental biology and medicine (Maywood, N.J.) 36 12192108
2014 Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways. PloS one 35 25546419
2003 Association of Eotaxin gene family with asthma and serum total IgE. Human molecular genetics 35 12761043
1998 Expression and participation of eotaxin during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granuloma formation. Journal of immunology (Baltimore, Md. : 1950) 35 9780203
2011 Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes. Journal of biomedical science 34 22114952
2004 Expression of rat I-TAC/CXCL11/SCYA11 during central nervous system inflammation: comparison with other CXCR3 ligands. Laboratory investigation; a journal of technical methods and pathology 34 15322564
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2014 Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation. International forum of allergy & rhinology 31 24989688
2001 Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia. The European respiratory journal 31 11488333
2013 Control of extravillous trophoblast function by the eotaxins CCL11, CCL24 and CCL26. Human reproduction (Oxford, England) 30 23477905
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