Affinage

CCL8

C-C motif chemokine 8 · UniProt P80075

Length
99 aa
Mass
11.2 kDa
Annotated
2026-04-28
96 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL8 (MCP-2) is a CC chemokine that functions as a broad-spectrum leukocyte chemoattractant, orchestrating innate and adaptive immune cell recruitment in inflammation, infection, tissue repair, and tumor microenvironment remodeling. Originally isolated as a monocyte-selective chemoattractant (PMID:1613466), CCL8 signals through multiple CC chemokine receptors—CCR1, CCR2, CCR3, CCR5, and in mice CCR8—via pertussis toxin-sensitive G-protein pathways to recruit monocytes, T lymphocytes (CD4+, CD8+, γ/δ, Treg), eosinophils, basophils, NK cells, and hematopoietic progenitors (PMID:7926371, PMID:9115216, PMID:9790730, PMID:21217759, PMID:24477914, PMID:27471618). CCL8 transcription is induced by IFN-γ (synergizing with IL-1β or TLR ligands) through a defined promoter region and is regulated by STAT1, IRF1, JMJD1A-mediated H3K9me2 demethylation at its promoter, ERK/p38 MAPK stabilization of its mRNA, and repressed by BLIMP1 and microRNAs (miR-146a, miR-92a, miR-345-5p) targeting its 3′ UTR (PMID:10496322, PMID:18981157, PMID:24477914, PMID:29550454, PMID:30841468, PMID:41779805). Extracellular proteolytic truncation of full-length CCL8(1–76) to CCL8(6–75) converts it from an agonist to a CCR2-selective antagonist that blocks ERK signaling and induces receptor internalization, establishing a built-in negative regulatory mechanism (PMID:19224633).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 High

    The identity of CCL8 as a distinct monocyte chemoattractant was unknown; its purification and sequencing established it as a novel CC chemokine structurally related to MCP-1 with selective monocyte-recruiting activity.

    Evidence Protein purification from osteosarcoma supernatants, peptide sequencing, Boyden chamber chemotaxis, intradermal injection in rabbits

    PMID:1613466

    Open questions at the time
    • Receptor identity unknown
    • Mechanism of monocyte selectivity undefined
    • In vivo physiological role not tested
  2. 1994 High

    Whether CCL8 acted on cell types beyond monocytes was uncertain; demonstration that it attracts CD4+ and CD8+ T cells, eosinophils, and basophils via pertussis toxin-sensitive GPCRs and cross-desensitizes with MCP-1/RANTES receptors revealed it as a broad-spectrum chemoattractant with overlapping receptor usage.

    Evidence Boyden chamber chemotaxis, Ca2+ flux, pertussis toxin inhibition, cross-desensitization on T cells, eosinophils, and basophils

    PMID:7514401 PMID:7531149 PMID:7535823 PMID:7926371

    Open questions at the time
    • Specific receptor identities not molecularly defined
    • Relative receptor preference hierarchy unknown
  3. 1997 High

    The molecular identity of CCL8 receptors was resolved by demonstrating direct high-affinity binding to CCR1 and CCR2B in transfected cells with functional chemotactic responses.

    Evidence Radioligand binding and chemotaxis in CCR1- and CCR2B-transfected HEK293 cells

    PMID:9115216

    Open questions at the time
    • CCR3 and CCR5 interactions not yet characterized
    • In vivo receptor preference not determined
  4. 1998 High

    Whether CCL8 engaged CCR5 was unknown; binding and functional assays demonstrated high-affinity CCR5 agonism, HIV-1 gp120 competition, and preferential CCR5 use on activated T cells, expanding the receptor repertoire.

    Evidence Radioligand binding to CCR5 transfectants, gp120 competition, anti-CCR5 mAb blocking, chemotaxis

    PMID:9790730

    Open questions at the time
    • CCR3 affinity not quantitated
    • Physiological relevance of HIV coreceptor blocking not tested in vivo
  5. 1999 High

    The transcriptional regulation of CCL8 was undefined; promoter deletion mapping identified an IFN-γ-responsive element between −340 and −301 and demonstrated synergistic induction by IFN-γ plus IL-1β.

    Evidence Luciferase reporter assays, EMSA in fibroblasts and osteosarcoma cells

    PMID:10496322

    Open questions at the time
    • Specific transcription factors binding the element not identified
    • Post-transcriptional regulation unexplored
  6. 2008 High

    The signaling pathways controlling CCL8 mRNA accumulation were clarified: oncostatin M induces CCL8 via ERK1/2-driven c-Jun/c-Fos transcription and p38-mediated mRNA stabilization through tristetraprolin inhibition.

    Evidence MAPK inhibitors, siRNA knockdown of c-Jun/c-Fos, mRNA stability assays in dermal fibroblasts

    PMID:18981157

    Open questions at the time
    • Whether this pathway operates in macrophages or other major CCL8 producers unknown
    • Direct tristetraprolin-CCL8 mRNA interaction not shown
  7. 2009 High

    A key question was whether CCL8 activity is modulated post-secretion; discovery that extracellular processing truncates CCL8(1–76) to CCL8(6–75), converting it from agonist to CCR2 antagonist, established a built-in negative feedback mechanism.

    Evidence N-terminal sequencing of truncated forms, Ca2+ and ERK signaling via CCR1/2/3/5 transfectants, chemotaxis, receptor internalization assays

    PMID:19224633

    Open questions at the time
    • Identity of the responsible protease not determined
    • In vivo relevance of truncated form not demonstrated
  8. 2011 High

    Species-specific receptor usage was resolved when mouse CCL8 was shown to be a CCR8 agonist (not CCR2), recruiting Th2 cells to allergen-inflamed skin, with Ccl8−/− and Ccr8−/− mice showing reduced eosinophilic inflammation.

    Evidence Ccl8−/− and Ccr8−/− mouse atopic dermatitis models, adoptive transfer, receptor signaling assays

    PMID:21217759

    Open questions at the time
    • Whether human CCL8 also signals through CCR8 not established
    • Structural basis for species-specific receptor selectivity unknown
  9. 2014 High

    Whether CCL8 transcription is tonically repressed was answered by showing BLIMP1 directly represses CCL8 in macrophages; Ccl8−/− mice demonstrated CCL8 recruits γ/δ T cells producing IL-17F for Listeria clearance.

    Evidence Conditional Blimp1 KO macrophages, transcriptome analysis, Ccl8−/− mice, Listeria infection, γ/δ T cell depletion

    PMID:24477914

    Open questions at the time
    • BLIMP1 binding site on CCL8 promoter not mapped
    • Mechanism of γ/δ T cell chemotaxis to CCL8 (receptor identity) not defined
  10. 2014 Medium

    Post-transcriptional control of CCL8 by miRNAs was established: miR-146a targets CCL8 3′ UTR in microglia during HIV infection, and miR-92a suppression by HCMV LAcmvIL-10 de-represses CCL8 during viral latency.

    Evidence miRNA overexpression in primary microglial cells (PMID:20181935), secretome proteomics in myeloid progenitors (PMID:25253336)

    PMID:20181935 PMID:25253336

    Open questions at the time
    • miR-146a direct luciferase validation for CCL8 not shown in the 2010 study
    • Quantitative contribution of miRNA regulation vs. transcriptional induction not compared
  11. 2018 Medium

    CCL8 was placed in visceral pain circuitry: spinal CCL8 acting through CCR5/ERK mediates colitis-induced hyperalgesia, and miR-146a-5p directly targets CCL8 3′ UTR (confirmed by dual-luciferase) to suppress this pathway.

    Evidence Dual-luciferase reporter assay, intrathecal CCL8 siRNA and miR-146a agomir, colorectal distension pain threshold in TNBS colitis model

    PMID:29037608 PMID:29550454

    Open questions at the time
    • Cell type producing spinal CCL8 (neuron vs. glia) not definitively resolved
    • Whether CCL8/CCR5 pain signaling operates in humans unknown
  12. 2019 Medium

    CCL8's role in tumor immune microenvironments was mechanistically dissected: hypoxia-induced ZEB1 activates CCL8 transcription in cancer cells to recruit macrophages via CCR2/NF-κB, and miR-345-5p directly targets CCL8 3′ UTR to restrain pancreatic cancer NF-κB-driven proliferation.

    Evidence Macrophage migration assays, luciferase reporter for miR-345-5p, NF-κB pathway analysis in cervical and pancreatic cancer models

    PMID:30841468 PMID:31263103

    Open questions at the time
    • Whether ZEB1 directly binds CCL8 promoter not shown by ChIP
    • NF-κB activation downstream of CCL8 lacks receptor specificity assignment
  13. 2021 Medium

    CCL8's pro-fibrotic function was established: CCL8 stimulates collagen production in fibroblasts via ERK1/2, and anti-CCL8 antibody reduces fibrosis in an IgG4-related disease model.

    Evidence Recombinant CCL8 stimulation, Western blot for collagen and p-ERK1/2, anti-CCL8 antibody in LAT Y136F knockin mice

    PMID:34391459

    Open questions at the time
    • Receptor mediating fibrotic CCL8 signaling in fibroblasts not identified
    • Whether CCL8 drives fibrosis independently of immune cell recruitment not resolved
  14. 2022 Medium

    CCL8 was shown to drive a self-amplifying macrophage-monocyte recruitment loop in kidney allografts: donor macrophage CCL8 recruits recipient monocytes that differentiate and produce more CCL8, then recruit CCR8+ T cells; blocking CCL8-CCR8 reduces graft inflammation.

    Evidence Allogeneic murine kidney transplant, CCL8-CCR8 blocking antibody, macrophage depletion, flow cytometry

    PMID:35973731

    Open questions at the time
    • Relative contribution of CCR2 vs. CCR8 in monocyte vs. T cell recruitment not dissected
    • Human relevance not tested
  15. 2023 Medium

    A tumor-metabolic axis for CCL8 was defined: lactate from tumor cells induces CCL8 in M2 macrophages via AKT/ERK, and CCL8 activates CCR5/mTORC1 on colorectal cancer cells to promote metastasis.

    Evidence RNA-seq, CCR5 knockdown/antagonist, allograft mouse model, colony formation and wound healing assays

    PMID:38136340

    Open questions at the time
    • Whether mTORC1 is the direct effector or requires intermediate signaling steps unknown
    • Single study without independent replication
  16. 2025 Medium

    Epigenetic and transcriptional control of CCL8 was deepened: JMJD1A/STAT1/IRF1 demethylate H3K9me2 at the CCL8 promoter in colonic epithelium during infection; HSP90 stabilizes STAT1 to drive CCL8 in atrial cardiomyocytes; senescent cell-derived CCL8 recruits cytotoxic CD8+ T cells to infarcted hearts.

    Evidence JMJD1A−/− mice with ChIP at CCL8 promoter (PMID:41779805); HSP90 inhibitor/STAT1 knockdown in HL-1 cells (PMID:41720180); p16-CreER mice with CCL8 neutralization and CD8 depletion post-MI (PMID:41766526)

    PMID:41720180 PMID:41766526 PMID:41779805

    Open questions at the time
    • Whether JMJD1A-IRF1 axis is specific to CCL8 or co-regulates other chemokines not tested
    • STAT1 vs. IRF1 hierarchy in different cell types not resolved
    • Therapeutic window for CCL8 blockade in cardiac repair unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the protease that truncates CCL8(1–76) to the antagonist CCL8(6–75) in vivo remains unknown, as does the structural basis for species-specific receptor selectivity (human CCR1/2/3/5 vs. mouse CCR8); a comprehensive understanding of how CCL8 receptor choice is determined in different tissue microenvironments is lacking.
  • Protease identity for N-terminal truncation not determined
  • Structural basis for mouse CCR8 vs. human CCR2 selectivity not resolved
  • No crystal structure of CCL8-receptor complex available

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 3
Partners
BLIMP1CCR1CCR2CCR3CCR5CCR8IRF1STAT1

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CCL8 (MCP-2) was isolated and characterized as a novel CC chemokine that specifically attracts monocytes but not neutrophils in vitro and in vivo, with a primary structure closely related to MCP-1, establishing it as a monocyte chemoattractant. Protein purification, peptide sequencing, Boyden chamber chemotaxis assay, intradermal injection in rabbits The Journal of experimental medicine High 1613466
1997 CCL8 (MCP-2) uses CCR1 and CCR2B as its functional receptors, as demonstrated by radioiodinated MCP-2 binding to CCR1- and CCR2B-transfected HEK293 cells, competitive displacement, and chemotaxis of transfected cells. Radioligand binding assay, receptor-transfected cell chemotaxis, competitive displacement The Journal of biological chemistry High 9115216
1994 CCL8 (MCP-2) attracts human CD4+ and CD8+ T lymphocytes, induces Ca2+ flux via pertussis toxin-sensitive G-protein-coupled receptors, and shares receptors with MCP-1 and MCP-3 as shown by cross-desensitization experiments. Boyden chamber chemotaxis, cytosolic Ca2+ measurement, pertussis toxin treatment, receptor desensitization assay FASEB journal High 7926371
1995 CCL8 (MCP-2) activates human basophils and eosinophils, inducing Ca2+ transients, chemotaxis, and mediator release. Cross-desensitization showed CCL8 interacts with receptors for both MCP-1 and RANTES. In IL-3-untreated basophils, MCP-2 acts as a functional inhibitor of CC chemokine actions. Basophil/eosinophil activation assay, Ca2+ measurement, chemotaxis, receptor desensitization Journal of immunology High 7535823
1995 CCL8 (MCP-2) acts on human monocytes to induce migration and N-acetyl-beta-D-glucosaminidase release. Cross-desensitization and competitive binding studies showed MCP-2 shares receptors with MCP-1, MCP-3 and also interacts with RANTES/MIP-1 receptors, but not vice versa. Monocyte migration assay, enzyme release assay, Ca2+ measurement, radiolabeled MCP-1 and MIP-1alpha binding competition European journal of immunology High 7531149
1994 CCL8 (MCP-2) attracts human eosinophils and cross-desensitizes eosinophil chemotaxis towards RANTES, suggesting CCL8 signals through the RANTES receptor on eosinophils. Boyden chamber eosinophil chemotaxis, cross-desensitization experiments Biochemical and biophysical research communications Medium 7514401
1998 CCL8 (MCP-2) binds CCR5 with high affinity, acts as a true CCR5 agonist eliciting chemotaxis and Ca2+ flux in CCR5 transfectants, blocks HIV-1 gp120 binding to CCR5, and preferentially uses CCR5 (over CCR1 or CCR2) on activated T cells. Radioligand binding to CCR5 transfectants, chemotaxis assay, Ca2+ flux, gp120 competition assay, anti-CCR5 mAb blocking Cellular immunology High 9790730
1994 CCL8 (MCP-2) is chemically synthesized into a biologically active 76-residue chemokine with correct disulfide bridges, is chemotactic for monocytes at ~7.5 ng/ml (comparable to natural MCP-2), and does not induce neutrophil chemotaxis. Chemical synthesis (Fmoc chemistry), RP-HPLC purification, SDS-PAGE, disulfide bridge formation, monocyte chemotaxis assay Journal of immunology High 8189067
1995 Synthetic CCL8 (MCP-2) co-elutes and co-migrates with natural MCP-2, has monocyte chemotactic activity at 7.5 ng/ml, and does not attract neutrophils, confirming that the 76-residue folded structure is sufficient for biological activity. Chemical synthesis, RP-HPLC, SDS-PAGE, monocyte and neutrophil chemotaxis Cytokine High 7780043
1997 The CCL8 gene (SCYA8) was cloned from chromosome 17q11.2, has a conserved three-exon/two-intron structure shared with MCP-1 and MCP-3, and produces a 1.0-kb mRNA predominantly in small intestine, peripheral blood, heart, placenta, lung, skeletal muscle, ovary, colon, and spinal cord. YAC contig PCR cloning, gene sequencing, Northern blot analysis Genomics High 9119400
1999 IFN-gamma induces CCL8 (MCP-2) transcription in fibroblasts through a promoter region between -340 and -301 (relative to transcription start), containing elements recognized by transcription factors identified by EMSA; IL-1beta alone was insufficient but synergized with IFN-gamma for additional induction. Promoter deletion/luciferase reporter assay, electrophoretic mobility shift assay (EMSA), transfection into diploid fibroblasts and osteosarcoma cells Journal of leukocyte biology High 10496322
2000 MMP-9 (gelatinase B) does not cleave CCL8 (RANTES and MCP-2 are left intact by gelatinase B), in contrast to its processing of IL-8 and degradation of CTAP-III, PF-4, and GRO-alpha. In vitro protease cleavage assay with purified MMP-9 and chemokines, functional neutrophil activation assays Blood High 11023497
2009 CCL8 (MCP-2) is synergistically induced by combined IFN-gamma + IL-1beta (or IFN-gamma + TLR ligands) in fibroblasts and endothelial cells. The intact CCL8(1-76) is processed into CCL8(6-75) by an extracellular protease, losing chemotactic activity but retaining receptor occupancy and acting as a CCR2 antagonist that inhibits MCP-1/CCL2 and MCP-2 ERK signaling and induces CCR2 internalization. Cytokine induction assay, N-terminal sequencing of truncated forms, Ca2+ signaling via CCR1/2/3/5-transfected cells, ERK signaling, chemotaxis assay, receptor internalization European journal of immunology High 19224633
2011 Mouse CCL8 is an agonist for CCR8 (but not CCR2), recruiting IL-5-enriched CCR8+ Th2 cells to allergen-inflamed skin. Ccr8- and Ccl8-deficient mice had markedly reduced eosinophilic inflammation in an atopic dermatitis model, and adoptive transfer confirmed CCR8 as key for Th2 cell skin recruitment. CCR8/CCR2 signaling assay, Ccl8-/- and Ccr8-/- mouse models, adoptive transfer, chronic atopic dermatitis model, flow cytometry Nature immunology High 21217759
2010 CCL8/MCP-2 is a direct target of miR-146a in HIV-1-infected human microglial cells; overexpression of miR-146a prevented HIV-induced CCL8 secretion, consistent with miR-146a binding the CCL8 3' UTR. miRNA overexpression in primary microglial cells, ELISA for CCL8, HIV-1 infection model, analysis of HIVE brain samples FASEB journal Medium 20181935
2014 The viral HCMV protein LAcmvIL-10 suppresses cellular miRNA hsa-miR-92a, which directly targets the CCL8 3' UTR; loss of hsa-miR-92a de-represses CCL8, increasing its secretion during HCMV latent infection of myeloid progenitor cells. Primary myeloid progenitor cell latency model, miRNA analysis, secretome proteomics, functional linkage of LAcmvIL-10 to miR-92a to CCL8 Journal of virology Medium 25253336
2013 Mycobacterium infection induces CCL8/MCP-2 production in macrophages through TLR2/PI3K/Akt and p38 signaling pathways; CCL8 accumulates in TB pleural effusions and its primary receptor CCR5 is expressed on pleural CD4+ T cells. BCG and M. tuberculosis infection of macrophage cell lines and primary MDMs, signaling inhibitor studies, protein array, qPCR PloS one Medium 23418602
2014 BLIMP1 directly represses CCL8 transcription in macrophages. BLIMP1-deficient macrophages express elevated CCL8; CCL8 is chemotactic for γ/δ T cells enriched for IL-17F, and CCL8-mediated Listeria clearance is dependent on γ/δ T cells. Conditional Blimp1 KO macrophages, transcriptome analysis, Ccl8-/- mice, Listeria monocytogenes infection model, γ/δ T cell depletion Journal of immunology High 24477914
2008 Oncostatin M stimulates CCL8 expression in primary human dermal fibroblasts via ERK1/2 and p38 MAPK pathways (through c-Jun and c-Fos as ERK targets); p38 prolongs CCL8 mRNA half-life by inhibiting tristetraprolin. CCL8 is not regulated by STAT1, STAT3, or STAT5, but STAT5/CIS axis selectively represses CCL1 (not CCL8). Cytokine stimulation, MAPK inhibitors, siRNA knockdown of c-Jun/c-Fos/STATs, mRNA stability assays, migration assays Journal of immunology High 18981157
2017 CCL8 interacts with CCR3 with a dissociation constant of ~1.2 × 10^-7 M measured by quartz crystal microbalance; CCL8 induces CCR3 internalization in vivo within 1 hour and elicits weaker chemotaxis of CCR3-expressing cells compared to CCL11 and CCL24. Quartz crystal microbalance (QCM) binding assay, CCR3 internalization assay, transwell chemotaxis assay BMC immunology Medium 29281969
2005 TRAIL pretreatment abrogates TNF-alpha-induced CCL8 and CXCL10 upregulation in endothelial cells via TRAIL-R1 and TRAIL-R2, and exogenous CCL8 plus CXCL10 restores the proadhesive activity of TNF-alpha, establishing that CCL8 is a key mediator of TNF-alpha-induced leukocyte adhesion to endothelium. cDNA microarray, neutralizing antibody rescue experiments, agonistic anti-TRAIL receptor antibodies, HL-60 adhesion assay Blood Medium 15644410
2016 CCL8 drives Treg recruitment to metastatic lungs via CCR5 signaling; F4/80+ macrophages in metastatic lungs produce CCL8, Tregs in metastatic lungs are enriched for CCR5, and Maraviroc (CCR5 inhibitor) reduces CCL8-driven Treg migration ex vivo and reduces metastatic tumor burden in vivo. Flow cytometry, ex vivo Treg migration toward CCL8, CCR5 inhibitor treatment, metastatic mouse tumor model Oncoimmunology Medium 27471618
2019 Hypoxia-induced ZEB1 in cervical cancer cells activates CCL8 transcription, which then attracts macrophages via the CCR2-NF-κB pathway, promoting tumor-associated macrophage accumulation and cancer progression. In vitro macrophage migration assay, chemokine expression array, mechanistic follow-up of ZEB1-CCL8-CCR2 axis Cell death & disease Medium 31263103
2019 miR-345-5p directly targets the CCL8 3' UTR (confirmed by luciferase assay), suppressing CCL8 expression; CCL8 activates NF-κB signaling to promote pancreatic cancer cell proliferation and invasion. Luciferase reporter assay, Western blot, Transwell invasion, NF-κB pathway analysis Biomedicine & pharmacotherapy Medium 30841468
2018 miR-146a-5p directly targets the 3' UTR of CCL8 (confirmed by dual-luciferase reporter assay) in spinal neurons; CCL8 upregulation in the spinal cord mediates visceral pain via CCR5/ERK activation, and intrathecal CCL8 siRNA or miR-146a-5p agomir reduces colitis-induced visceral hyperalgesia. Dual-luciferase reporter assay, intrathecal injection, siRNA knockdown, neutralizing antibody, colorectal distension pain threshold measurement Brain research bulletin Medium 29550454
2017 CCL8 and its receptor CCR5 are upregulated in the spinal cord following colitis (TNBS model); intrathecal CCL8 neutralizing antibody or CCR5 antagonist reduces visceral hyperalgesia and spinal ERK activation, placing CCL8/CCR5/ERK in a visceral pain signaling pathway. TNBS colitis mouse model, intrathecal antibody/antagonist injection, ERK phosphorylation assay, MEK inhibitor treatment, pain behavioral testing Brain research bulletin Medium 29037608
2022 In a murine kidney transplant model, donor kidney resident macrophages upregulate CCL8 post-transplant, which promotes recipient monocyte graft infiltration, monocyte differentiation to resident macrophages (further expressing CCL8), and subsequent CCR8+ T cell infiltration; blocking CCL8-CCR8 or depleting donor macrophages reduces early allograft inflammation and improves graft function. Allogeneic murine kidney transplant model, CCL8-CCR8 blocking antibody, macrophage depletion, flow cytometry Journal of the American Society of Nephrology Medium 35973731
2023 Lactate induces CCL8 production in M2 tumor-associated macrophages via AKT/ERK signaling; secreted CCL8 then activates CCR5 on colorectal cancer cells, triggering mTORC1 signaling to promote proliferation and metastasis; CCR5 antagonism or knockdown blocks these effects. qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation, CCR5 knockdown/antagonist, allograft mouse model Cancers Medium 38136340
2021 CCL8 stimulates collagen production in fibroblasts via ERK1/2 phosphorylation; anti-CCL8 neutralizing antibody treatment in an IgG4-RD mouse model reduces salivary gland inflammation and fibrosis scores. Recombinant CCL8 stimulation of NIH/3T3 fibroblasts, Western blot for collagen and p-ERK1/2, anti-CCL8 antibody treatment in LAT Y136F knockin mice Arthritis research & therapy Medium 34391459
2022 F. nucleatum induces CCL8 expression in macrophages via TLR4/NF-κB signaling; iron attenuates the inhibitory phosphorylation of NF-κB p65 by activating serine/threonine phosphatases, thereby augmenting F. nucleatum-induced CCL8 production in tumor-associated macrophages. Macrophage infection assay, TLR4/NF-κB pathway inhibition, iron supplementation/depletion, Western blot for p-p65 JCI insight Medium 36136589
2010 Stromal cell-derived CCL8 cooperates with CXCL12 to attract hematopoietic progenitors that differentiate into regulatory dendritic cells; Leishmania donovani infection of bone marrow stromal cells enhances CCL8 production, increasing regulatory DC development. Murine leishmaniasis model, splenic stromal cell CCL8 production measurement, hematopoietic progenitor migration assay Journal of immunology Medium 20624948
2003 Mouse orphan receptor L-CCR expressed in HEK293 cells responds to CCL2, CCL7, CCL8, and CCL5 with pertussis toxin-sensitive chemotaxis and Ca2+ transients; biotinylated CCL2 binds to L-CCR-expressing cells, identifying L-CCR as a functional receptor for CCL8. Receptor transfection in HEK293, chemotaxis assay, Ca2+ measurement, pertussis toxin inhibition, biotinylated ligand binding Journal of leukocyte biology Medium 12885941
2020 CCL8 is upregulated in mast cells when co-cultured with endometrial cells; CCL8 promotes migration of endometrial epithelial and stromal cells and increases angiogenesis of endothelial cells; CCR1 (receptor for CCL8) is overexpressed in ectopic endometrium and co-localizes with blood vessels; CCR1 inhibition suppresses endometriosis development and angiogenesis in vivo. Mast cell-endometrial cell co-culture with mRNA sequencing, Transwell migration assay, CCK-8 proliferation, tube formation assay, mouse endometriosis model, CCR1 inhibition in vivo Biomedicine & pharmacotherapy Medium 32768961
2021 CCL8 deficiency in host mice receiving allogeneic bone marrow transplantation significantly reduces acute GVHD mortality (90% vs 23.4% survival), attenuates liver dysfunction and pathology, and is associated with a surge of plasma IL-6 in CCL8-/- recipients, suggesting CCL8 promotes GVHD pathogenesis potentially through IL-6 cascade. CCL8 knockout mice, allogeneic BMT model, survival analysis, histopathological scoring, cytokine ELISA Experimental hematology Medium 34808257
2014 Allergic airway inflammation decreases lung Klebsiella pneumoniae burden in a CCL8-dependent manner; neutralization of CCL8 reverses this protective effect, identifying a novel role for CCL8 in lung antibacterial immunity. Mouse allergic airway inflammation model, K. pneumoniae infection, CCL8 neutralizing antibody, bacterial burden measurement Infection and immunity Medium 24958709
2011 Dendritic cells express CCL8 upon stimulation by allogeneic CD4+ T cells through MHC class II molecule interactions (cell-contact dependent); the early plasma CCL8 level (day 5) after allogeneic BMT correlates with GVHD survival and pathological scores. Dendritic cell-T cell co-culture, anti-MHC class II blocking, allogeneic BMT mouse model, CCL8 immunoassay Experimental hematology Medium 21782767
2021 CCL8 secreted by ECFCs induces IL-8 production in TNBC cells via c-Jun transcription factor; IL-8 reciprocally induces CCL8 in ECFCs, forming a positive feedback loop that promotes invasion, angiogenesis, and tumorigenicity of both cell types. Indirect co-culture, cytokine antibody array, RT-PCR, siRNA knockdown, xenograft model Oncogene Medium 33833397
2025 In myocardial infarction, P16+ senescent fibroblasts and macrophages are the main sources of CCL8; CCL8 recruits cytotoxic CD8+ T cells and NK cells to the infarcted heart, promoting cardiomyocyte apoptosis and adverse remodeling. CCL8 blockade or Ccl8 deletion in P16+ cells reduces CD8+ T cell infiltration and improves cardiac repair. p16-CreER reporter mice, dual-recombinase intersectional ablation, scRNA-seq, bulk RNA-seq, CCL8 neutralization antibody, CD8+ T cell depletion, CellChat intercellular communication analysis Circulation High 41766526
2024 Muscle cell-derived (Pax7+, Myf5+, or MyoD+ myogenic progenitor cell) CCL8 negatively regulates myogenic differentiation; Cas9-mediated Ccl8 depletion in myogenic progenitor cells accelerates muscle regeneration after injury, and intramuscular recombinant CCL8 reverses this phenotype. Ccl8 knockdown in C2C12 myoblasts, AAV9-sgRNA Ccl8 gene editing in Pax7+/Myf5+/MyoD+ cells, barium chloride injury model, single-cell transcriptomics of existing datasets, recombinant CCL8 injection rescue FASEB journal Medium 39051762
2025 In esophageal cancer, CBX6 promotes CCL8 expression by interacting with SMARCD1 to remodel chromatin at the CCL8 promoter; CCL8 secretion leads to CD8+ T cell exhaustion and tumor progression. Cbx6 knockdown, co-culture with CD8+ T cells, chromatin remodeling assay, tissue microarray, in vivo tumorigenesis Cell biology and toxicology Low 41219497
2025 HSP90 interacts with transcription factor STAT1 and stabilizes it, driving CCL8 expression; STAT1 knockdown attenuates CCL8 upregulation and macrophage recruitment in atrial cardiomyocytes, placing HSP90-STAT1-CCL8 in a pathway mediating atrial inflammation during hypertension-induced atrial fibrillation. RNA sequencing, HSP90 inhibitor 17AAG, STAT1 knockdown, AngII mouse AF model, HL-1 cell line experiments Life sciences Medium 41720180
2025 USP18 stabilizes SOCS1 by inhibiting its ubiquitination and degradation, suppressing CCL8 production in alveolar type II epithelial cells through ERK-STAT3 signaling; USP18-deficient AT2 cells increase CCL8 expression, promoting Th2 cell and eosinophil recruitment; CCL8 knockdown in USP18 KO mice alleviates asthma symptoms. USP18 knockout mice, AT2-specific CCL8 knockdown, exogenous CCL8 treatment, SOCS1 ubiquitination assay, ERK-STAT3 pathway inhibition, Th2/eosinophil flow cytometry Respiratory research Medium 41354823
2025 JMJD1A (histone demethylase) cooperates with STAT1 to demethylate H3K9me2 on the IRF1 promoter, inducing IRF1 expression; IRF1 and JMJD1A together demethylate H3K9me2 on the CCL8 promoter to drive CCL8 expression in colonic epithelial cells, promoting macrophage and CD4+ T cell recruitment during enteric infection. JMJD1A-/- mice, C. rodentium infection, ChIP for H3K9me2, IRF1 overexpression/knockdown, macrophage depletion, mucosal immune cell analysis PLoS pathogens Medium 41779805
2025 miR-425 suppresses ZNF24 expression in astrocytes, which downregulates CCL8 secretion; reduced CCL8 leads to astrocyte activation that promotes breast cancer brain metastasis in vivo. miR-425 overexpression/inhibition in breast cancer EVs, astrocyte co-culture, ZNF24 knockdown, CCL8 ELISA, mouse brain metastasis model, immunohistochemistry International journal of molecular sciences Medium 41977380

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood 546 11023497
1992 Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. The Journal of experimental medicine 358 1613466
1994 Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 309 7926371
1995 Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes. European journal of immunology 308 7531149
1998 MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study. Journal of neuroimmunology 305 9655469
2011 Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2 cells. Nature immunology 257 21217759
2008 Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis. The European respiratory journal 155 18684849
2003 Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology (Baltimore, Md.) 153 14647058
1999 Expression of monocyte chemotactic protein (MCP)-1, MCP-2, and MCP-3 by human airway smooth-muscle cells. Modulation by corticosteroids and T-helper 2 cytokines. American journal of respiratory cell and molecular biology 122 10502563
1997 Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors. The Journal of biological chemistry 121 9115216
2019 Hypoxia-induced ZEB1 promotes cervical cancer progression via CCL8-dependent tumour-associated macrophage recruitment. Cell death & disease 109 31263103
2010 CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 107 20181935
1994 Induction of monocyte chemotactic proteins MCP-1 and MCP-2 in human fibroblasts and leukocytes by cytokines and cytokine inducers. Chemical synthesis of MCP-2 and development of a specific RIA. Journal of immunology (Baltimore, Md. : 1950) 107 8189067
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2025 Spatiotemporal mapping reveals Ccl8hi macrophages as key drivers of testicular inflammaging. Clinical and translational medicine 2 41251087
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2026 P16+ Cells Drive Adverse Postischemic Cardiac Remodeling Through CCL8-Mediated Recruitment of Cytotoxic Lymphocytes. Circulation 0 41766526
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2025 CBX6 induces CD8+ T cell exhaustion and tumor development in esophageal squamous cell carcinoma through SMARCD1-mediated CCL8 secretion and lactate efflux. Cell biology and toxicology 0 41219497
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2025 CCL8 suppresses ovarian cancer progression via M1 macrophage polarization and NF-κB-mediated apoptosis. Scientific reports 0 41408455