Affinage

CCL2

C-C motif chemokine 2 · UniProt P13500

Length
99 aa
Mass
11.0 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL2/MCP-1 is a secreted CC chemokine that orchestrates myeloid cell recruitment in inflammation, acting primarily through its receptor CCR2 to drive monocyte/macrophage chemotaxis, adhesion, and tissue infiltration (PMID:10227295, PMID:36752206). Under vascular flow it triggers firm adhesion of rolling monocytes to E-selectin-bearing endothelium, a function dissociable from calcium signaling and chemotaxis (PMID:10227295); in the chemotactic arm, CCR2 engagement signals through a calcium transient and a downstream PKCβ requirement that is genetically separable from the receptor-calcium step itself (PMID:12724308). CCL2 also binds oxidized LDL and Lp(a) via its basic residues Arg-18/Lys-19 while retaining monocyte-recruiting activity, linking the chemokine to lipoprotein-associated inflammation (PMID:23667177). Beyond leukocyte trafficking, CCL2/CCR2 supports osteoclastogenesis, acting upstream of DC-STAMP, NFATc1, calmodulin 1, JUN and NFATc2 at the apex of RANKL-driven differentiation (PMID:19364494, PMID:23996571), and mediates angiopoietin-1-dependent mural cell recruitment during angiogenesis (PMID:20571857). In parenchymal cells the chemokine engages a distinct, Gαi-independent ERK1/2 program that is cytoprotective in cardiomyocytes and neurons, lowering glutamate/NMDAR1-dependent excitotoxicity and apoptosis (PMID:16102724, PMID:19129402, PMID:12753088). CCL2 transcription is a highly regulated convergence point: it is positively driven by the atypical IκB family member IκBζ recruited to the proximal Ccl2 promoter with H3K4me3 deposition (PMID:23547114), by direct p53 binding required for TNF-α induction (PMID:20406462), and by Notch/RBPJ transactivation in hepatocytes that fuels macrophage recruitment and fibrosis in NASH (PMID:36752206); it is repressed by TGF-β1/Smad3 antagonism of AP-1 (PMID:14752027), by ATF3 binding ATF/CRE sites (PMID:24420912), and by estradiol-activated ERβ that sequesters Sp1/AP-1 activity (PMID:12787135). CCL2 contributes to inflammatory and pathological signaling in cancer invasion, neuroinflammatory pain, ethanol-induced developmental neuroapoptosis, and ischemia/reperfusion injury, generally through CCR2 and MAPK or PI3K/Akt effectors (PMID:29976212, PMID:29594759, PMID:25555372, PMID:31774703).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1999 High

    Established that CCL2 has an adhesion-promoting function on endothelium that is mechanistically distinct from its classical chemotactic role, expanding its action beyond chemotaxis.

    Evidence Flow chamber adhesion assay with receptor-transduced endothelial monolayers plus calcium imaging and chemotaxis controls

    PMID:10227295

    Open questions at the time
    • Receptor/signaling pathway mediating the adhesion effect not defined
    • Did not resolve which endothelial or monocyte molecules execute firm adhesion
  2. 2003 High

    Resolved the chemotactic signaling cascade by placing PKCβ downstream of the CCR2-triggered calcium response, separating the receptor-proximal calcium signal from the effector step needed for migration.

    Evidence Isoform-specific antisense knockdown plus PKC inhibitors and calcium measurement in human monocytes

    PMID:12724308

    Open questions at the time
    • Substrates of PKCβ in monocyte migration not identified
    • Link between calcium signal and PKCβ activation not mapped
  3. 2003 Medium

    Demonstrated CCL2 cytoprotection in CNS cells by lowering glutamate and NMDAR1 and identified RANTES neuroprotection as acting via MCP-1 induction, showing the chemokine has neuroprotective roles independent of leukocyte recruitment.

    Evidence Neuron/astrocyte apoptosis assays, glutamate measurement, NMDAR1 Western blot, anti-MCP-1 neutralization

    PMID:12753088

    Open questions at the time
    • Receptor and intracellular pathway for neuroprotection not defined in this study
    • In vitro mixed culture only
  4. 2003 Medium

    Identified opposing Smad control of CCL2 transcription: Smad-3 cooperates with HIV-1 Tat to stimulate the promoter while Smad-4 represses, mapping direct Smad-Tat interactions, advancing understanding of TGF-β/viral transcriptional input.

    Evidence MCP-1 promoter-luciferase reporters and Smad-Tat protein interaction/domain mapping in astrocytic cells

    PMID:12758167

    Open questions at the time
    • Endogenous promoter occupancy not shown
    • Context-dependence relative to Smad3 repression in macrophages unresolved
  5. 2003 High

    Defined an estrogen-dependent repression mechanism in which ERβ sequesters Sp1/AP-1 transcriptional activity at the CCL2 promoter without displacing their DNA binding, explaining hormonal suppression of the chemokine.

    Evidence Promoter-luciferase reporters, ERβ domain mutants, and co-IP of ERβ with Sp1/AP-1 in keratinocytes

    PMID:12787135

    Open questions at the time
    • In vivo relevance of ERβ-CCL2 axis not tested
    • Quantitative contribution of Sp1 vs AP-1 not separated
  6. 2004 High

    Pinpointed Smad3 as the obligate mediator of TGF-β1 repression of CCL2 in macrophages through antagonism of AP-1 DNA binding, with in vivo arteriopathy consequences, defining a key negative transcriptional brake.

    Evidence Smad3 gain-of-function, Smad3-KO macrophages, AP-1 binding assay, and cardiac allograft model

    PMID:14752027

    Open questions at the time
    • Mechanism of Smad3-AP-1 antagonism (sequestration vs competition) not fully resolved
    • Promoter elements bound not mapped
  7. 2005 Medium

    Showed cytoprotective and chemotactic CCL2 functions use distinct receptor-coupled pathways, with ERK1/2 (not Gαi) mediating anti-apoptotic protection of cardiomyocytes, formally bifurcating CCL2 signaling outputs.

    Evidence Cardiomyocyte hypoxia apoptosis assays with ERK and Gαi (pertussis toxin) inhibitors and Bcl-2 family Western blots

    PMID:16102724

    Open questions at the time
    • Receptor coupling ERK in cardiomyocytes not identified
    • In vitro hypoxia model only
  8. 2006 Medium

    Mapped a PKC→NF-κB pathway driving high-glucose/hyperosmolarity induction of CCL2 in mesothelial cells, distinguishing it from MAPK routes and showing glucocorticoid suppression via IκBα.

    Evidence Systematic pharmacological pathway dissection, NF-κB EMSA, and MCP-1 RT-PCR/ELISA in rat mesothelial cells

    PMID:16518329

    Open questions at the time
    • Direct promoter occupancy by NF-κB not shown
    • Single-cell-type in vitro context
  9. 2008 Medium

    Extended the inducer repertoire by showing lipoxygenase product 12(S)-HETE and the myelin-deficient Schwann cell state drive CCL2 through PKC/p38/NADPH oxidase and MEK-ERK respectively, linking lipid and neural-injury signals to chemokine output.

    Evidence 12/15-LO KO/transgenic mice and macrophage lines; MEK inhibitor CI-1040 in Schwann cells and P0+/- nerves

    PMID:18296557 PMID:18383340

    Open questions at the time
    • Transcription factor endpoints downstream of these kinases not identified
    • Whether pathways converge on shared promoter elements unknown
  10. 2009 Medium

    Established CCL2 as an apical, autocrine driver of RANKL-induced osteoclastogenesis acting upstream of DC-STAMP, NFATc1, and cathepsin K, defining a non-immune developmental role for the chemokine.

    Evidence MCP-1-KO osteoclast cultures with recombinant rescue and DC-STAMP-KO epistasis; RT-PCR of differentiation markers

    PMID:19364494

    Open questions at the time
    • Receptor on osteoclast precursors not confirmed
    • Single-lab in vitro epistasis
  11. 2009 High

    Connected adrenergic input to CCL2 neuroprotection, showing β2-AR/cAMP induces astrocytic CCL2 that lowers NMDA-dependent glutamate release and calcium entry to protect neurons across multiple injury paradigms.

    Evidence Primary co-cultures, MCP-1 promoter reporter, β2-AR antagonist, anti-MCP-1 neutralization, calcium/LDH/OGD readouts

    PMID:19129402

    Open questions at the time
    • Neuronal receptor transducing the protective signal not identified
    • In vivo neuroprotection not tested
  12. 2010 High

    Demonstrated CCL2/CCR2 is required for angiopoietin-1-driven mural cell recruitment during angiogenesis, broadening its role to vascular wall assembly.

    Evidence Aortic ring model with MCP-1-KO and CCR2-KO mice, anti-MCP-1 blockade, recombinant MCP-1, and p38 inhibitor

    PMID:20571857

    Open questions at the time
    • Mural cell receptor/signaling response not fully defined
    • Relationship to monocyte recruitment in the same model not separated
  13. 2010 High

    Identified p53 as a direct transcriptional activator binding a defined upstream site required for TNF-α-induced CCL2, with HPV E6-mediated p53 loss abolishing induction, adding tumor-suppressor control of the chemokine.

    Evidence EMSA and ChIP for p53 binding, siRNA knockdown, and multiple genetic keratinocyte/Li-Fraumeni systems

    PMID:20406462

    Open questions at the time
    • Cofactors enabling p53 at the CCL2 promoter not defined
    • Generality beyond keratinocytes not established
  14. 2013 High

    Defined IκBζ as a direct positive regulator recruited to the proximal Ccl2 promoter that deposits activating H3K4me3 and is needed for LPS/peptidoglycan-induced secretion and monocyte infiltration in vivo.

    Evidence IκBζ-KO macrophages, ChIP for occupancy and H3K4me3, and in vivo peritonitis

    PMID:23547114

    Open questions at the time
    • How IκBζ cooperates with NF-κB at the promoter not detailed
    • Histone methyltransferase recruited not identified
  15. 2013 High

    Mapped the lipoprotein-binding determinants of CCL2 to Arg-18/Lys-19 and showed the OxLDL/Lp(a)-bound chemokine retains monocyte-recruiting activity, mechanistically linking CCL2 to oxidized lipid carriers in plasma.

    Evidence Site-directed mutagenesis, OxLDL binding assays, E06 anti-OxPL blockade, plasma Lp(a) capture, and migration assays

    PMID:23667177

    Open questions at the time
    • Physiological consequence of lipoprotein-bound delivery in vivo not established
    • Effect on CCR2 affinity not quantified
  16. 2014 Medium

    Added ATF3 as a direct repressor binding ATF/CRE sites in the MCP-1 promoter and revealed exosomal ATF3 RNA as a trans-acting brake limiting macrophage recruitment after renal ischemia/reperfusion.

    Evidence ATF3-KO mice, I/R model, promoter binding assay, exosome transfer, and macrophage migration assay

    PMID:24420912

    Open questions at the time
    • Direct binding evidence relies on single-lab assays
    • Mechanism of exosomal ATF3 RNA action not detailed
  17. 2014 Medium

    Placed CCL2 induction at the apex of the RANKL osteoclastogenesis transcriptional cascade, with >1000-fold early induction preceding CALM1/JUN/NFATc2, refining pathway ordering established by earlier KO work.

    Evidence Human CFU-GM osteoclast differentiation with dominant-negative 7ND and temporal qPCR profiling

    PMID:23996571

    Open questions at the time
    • Receptor/signal driving the early transcriptional targets not defined
    • Single-lab temporal profiling
  18. 2014 Medium

    Extended CCL2/CCR2 signaling to neuroinflammatory pain via a PI3K/Akt-dependent spinal microglial activation mechanism with behavioral readout.

    Evidence Bone cancer pain rat model, microglia stimulation, PI3K inhibitor LY294002, intrathecal anti-MCP-1, and allodynia testing

    PMID:25555372

    Open questions at the time
    • Receptor identity on microglia not confirmed by genetics
    • Single-lab model
  19. 2014 Low

    Implicated MCP-1/CCR2 in ovarian cancer cell invasion and adhesion, suggesting tumor-cell-intrinsic chemokine signaling, though support rests on antagonist pharmacology alone.

    Evidence Transwell invasion/adhesion assays with CCR2 antagonist and CCR2 immunohistochemistry in SKOV-3 cells

    PMID:24222114

    Open questions at the time
    • Receptor antagonist only; no genetic confirmation
    • Single in vitro cell line
  20. 2018 Medium

    Defined a CCL2/CCR2→MEK/ERK axis driving triple-negative breast cancer invasion and EMT marker expression, linking autocrine chemokine signaling to tumor cell motility.

    Evidence Invasion assays with CCR2 antagonist, MEK inhibitor U0126, MCP-1 siRNA, and EMT marker Western blots

    PMID:29594759

    Open questions at the time
    • In vivo metastatic relevance not tested
    • Single-lab cell-line study
  21. 2018 High

    Established a pathogenic CCL2/CCR2 role in ethanol-induced developmental neuroapoptosis acting via TLR4 and GSK3β, using dual genetic and pharmacological tools.

    Evidence MCP-1-KO and CCR2-KO mice, neonatal ethanol model, Bindarit/RS504393 inhibitors, co-culture, and signaling analysis

    PMID:29976212

    Open questions at the time
    • Cell-type source vs target of CCL2 not fully separated
    • Direct link from CCR2 to TLR4 activation not mechanistically resolved
  22. 2019 Medium

    Resolved an intracellular consequence of CCL2/CCR2 in cardiomyocyte I/R injury, placing CaSR upstream of MCPIP1 to activate ER stress (not autophagy) and drive apoptosis.

    Evidence HL-1/primary cardiomyocyte simulated I/R with CCR2 and CaSR inhibitors/activators and ER stress Western blots

    PMID:31774703

    Open questions at the time
    • How CCR2 signaling engages CaSR not defined
    • In vitro only
  23. 2021 High

    Identified an adiponectin/APPL2-mTORC1 pathway that suppresses TNF-α-induced hepatocyte CCL2, defining a metabolic brake on chemokine-driven liver inflammation.

    Evidence Hepatocyte-specific APPL2-KO and adiponectin-KO double-KO epistasis on high-fat diet with mTORC1 analysis

    PMID:34162682

    Open questions at the time
    • Transcription factor endpoint downstream of mTORC1 at the Ccl2 promoter not identified
    • Mechanism of mTORC1-CCL2 link not detailed
  24. 2023 High

    Demonstrated hepatocyte-intrinsic Notch/RBPJ transactivation of the Ccl2 promoter as a driver of monocyte-derived macrophage recruitment and fibrosis in NASH, with cell-specific genetic and pharmacological proof.

    Evidence Hepatocyte-specific Ccl2-KO and Notch gain-of-function mice, CCR2 inhibitor, RBPJ promoter site analysis, and NASH fibrosis histology

    PMID:36752206

    Open questions at the time
    • Interaction of Notch/RBPJ with other CCL2 regulators not mapped
    • Human relevance shown only at promoter conservation level

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCL2's distinct functional outputs—adhesion, chemotaxis, parenchymal cytoprotection, osteoclast/mural cell programs—are selected at the level of receptor coupling and effector choice remains unresolved.
  • No structural basis for biased CCR2 signaling defined
  • Whether non-CCR2 receptors mediate adhesion and cytoprotection not established
  • In vivo significance of lipoprotein-bound CCL2 delivery not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0008289 lipid binding 1
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
CCR2LP(A)OXLDL

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MCP-1 (CCL2) rapidly triggers firm adhesion of rolling monocytes to vascular endothelium under flow conditions by acting on endothelium expressing E-selectin; this effect is independent of calcium transient induction or chemotaxis, revealing a distinct adhesion-promoting mechanism separate from classical chemotaxis. Flow chamber adhesion assay with endothelial monolayers transduced to express specific leukocyte-adherence receptors; calcium imaging Nature High 10227295
2003 CCL2/MCP-1 protects mixed cultures of human neurons and astrocytes from NMDA- or HIV-Tat-induced apoptosis by reducing extracellular glutamate levels and NMDA receptor 1 (NMDAR1) expression, and by decreasing intracellular Tat; the protective effect of RANTES was blocked by anti-MCP-1 antibody, indicating RANTES acts via induction of MCP-1. Cell culture apoptosis assay, extracellular glutamate measurement, NMDAR1 Western blot, anti-MCP-1 neutralizing antibody blockade, NMDA receptor blocker MK801 Journal of neurochemistry Medium 12753088
2003 PKCβ isoform is specifically required for MCP-1-induced chemotaxis of human monocytes; antisense knockdown of PKCβ caused ~89% inhibition of chemotaxis without affecting the MCP-1/CCR2-triggered calcium signal, placing PKCβ downstream of the initial receptor-calcium response in the chemotactic signaling cascade. Antisense oligodeoxyribonucleotide knockdown of specific PKC isoforms; PKC pharmacological inhibitors (GF109203X, Calphostin C); chemotaxis assay; calcium response measurement The Journal of biological chemistry High 12724308
2004 TGF-β1 inhibition of MCP-1 expression in macrophages is mediated specifically by Smad3; Smad3 overexpression potently repressed inducible MCP-1 expression, and TGF-β1 inhibition of cytokine-induced MCP-1 was completely lost in Smad3-deficient macrophages. Mechanistically, Smad3 antagonizes AP-1 (c-Jun/c-Fos) DNA binding and activity at the MCP-1 promoter. Adenoviral Smad3 overexpression; Smad3-knockout macrophages; AP-1 DNA-protein binding assay; cardiac allograft model with accelerated arteriopathy in Smad3-KO mice Circulation research High 14752027
2005 CCL2/MCP-1 protects cardiac myocytes from hypoxia-induced apoptosis through ERK1/2 signaling (not through Gαi, which mediates monocyte chemotaxis); CCL2 treatment decreased caspase-3 activation and JNK/SAPK phosphorylation, increased Bcl-xL and Bag-1, and decreased Bax, demonstrating cytoprotection and chemotaxis use distinct signaling pathways. Cardiac myocyte hypoxia apoptosis assay; ERK1/2 pathway inhibitor; Gαi inhibitor (pertussis toxin); Western blot for Bcl-2 family proteins, caspase-3, JNK/SAPK Biochemical and biophysical research communications Medium 16102724
2008 MCP-1 (CCL2) upregulation in P0-mutant (myelin-deficient) Schwann cells is mediated by the MEK1/2–ERK1/2 signaling pathway; MEK1/2 inhibitor CI-1040 reduced ERK1/2 phosphorylation and MCP-1 expression in Schwann cell lines in vitro and in peripheral nerves of P0+/− mice in vivo. Western blot of peripheral nerve lysates for phospho-ERK1/2 and phospho-MEK1/2; MEK1/2 inhibitor CI-1040 in vitro and systemic in vivo treatment; MCP-1 ELISA Glia Medium 18383340
2008 12(S)-HETE (a 12/15-lipoxygenase product) increases MCP-1 mRNA and protein expression in macrophages via PKC, p38 MAPK, and NADPH oxidase activity; genetic knockout of 12/15-LO reduced macrophage MCP-1 expression, while overexpression increased it. 12/15-LO knockout and transgenic mice; stable 12/15-LO overexpressing macrophage cell line; pharmacological inhibitors of PKC, p38, and NADPH oxidase; MCP-1 ELISA and RT-PCR American journal of physiology. Heart and circulatory physiology High 18296557
2009 Noradrenaline induces MCP-1 expression in astrocytes via β2-adrenergic receptor and cAMP signaling, and this astrocyte-derived MCP-1 reduces NMDA-dependent glutamate release and Ca2+ entry in neurons, thereby mediating neuroprotection; neutralizing antibody to MCP-1 blocked conditioned medium-mediated protection, and MCP-1 dose-dependently reduced neuronal damage from NMDA, glutamate, and oxygen-glucose deprivation. Primary astrocyte and neuron cultures; MCP-1 promoter-luciferase reporter; β2-adrenergic receptor antagonist; cAMP analog; neutralizing anti-MCP-1 antibody; intracellular Ca2+ measurement; LDH release assay; ATP measurement; oxygen-glucose deprivation model The Journal of neuroscience High 19129402
2009 MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner under RANKL stimulation; MCP-1-deficient osteoclast precursors showed impaired multinuclear osteoclast formation, downregulation of DC-STAMP, NFATc1, and cathepsin K, and these defects were rescued by recombinant MCP-1 but not by rescuing DC-STAMP, indicating MCP-1 acts upstream of DC-STAMP in the osteoclastogenesis pathway. MCP-1 knockout mouse osteoclast cultures; recombinant MCP-1 rescue; DC-STAMP-deficient mouse cells; RT-PCR for osteoclast differentiation markers Biochemical and biophysical research communications Medium 19364494
2010 MCP-1 promotes mural cell recruitment during angiogenesis; angiopoietin-1-induced mural cell recruitment requires MCP-1 (anti-MCP-1 antibody blocks Ang-1 effect), and aortic rings from MCP-1-knockout or CCR2-knockout mice have fewer mural cells; recombinant MCP-1 dose-dependently increases mural cell number. Aortic ring angiogenesis model; MCP-1 and CCR2 knockout mice; anti-MCP-1 blocking antibody; recombinant MCP-1 addition; p38 MAPK inhibitor Angiogenesis High 20571857
2013 MCP-1 binds to oxidized LDL (OxLDL) via basic amino acid residues Arg-18 and Lys-19; mutation of these residues abolished OxLDL binding. OxLDL-bound MCP-1 retains monocyte-recruiting activity. MCP-1 also binds Lp(a) in human plasma through oxidized phospholipids (OxPLs), as demonstrated by E06 monoclonal antibody (anti-OxPL) inhibition. Site-directed mutagenesis (Arg18Ala/Lys19Ala); OxLDL binding assay; E06 monoclonal antibody inhibition; recombinant MCP-1 spiking into human plasma; Lp(a) capture and MCP-1 ELISA; monocyte migration assay Journal of lipid research High 23667177
2013 IκBζ, an atypical IκB family member, is a key transcriptional activator of the Ccl2 (MCP-1) gene; IκBζ-deficient macrophages show impaired CCL2 secretion in response to LPS or peptidoglycan, IκBζ is directly recruited to the proximal Ccl2 promoter (by ChIP), and promotes transcription-enhancing H3K4me3 histone marks. In vivo, IκBζ-KO mice show impaired CCL2 secretion and monocyte infiltration in peritonitis. IκBζ-knockout macrophages; ELISA for CCL2; chromatin immunoprecipitation (ChIP) for IκBζ occupancy and H3K4me3; in vivo peritonitis model Journal of immunology High 23547114
2014 ATF3 binds ATF/CRE sites in the MCP-1 promoter and transcriptionally represses MCP-1 expression in renal epithelial cells after ischemia/reperfusion (I/R) injury; ATF3-knockout mice showed higher MCP-1 induction after I/R. Exosomal ATF3 RNA from epithelial cells also inhibited MCP-1 expression and macrophage migration. ATF3 knockout mice; I/R injury model; chromatin immunoprecipitation/promoter binding assay for ATF3 at MCP-1 promoter; exosome isolation and transfer; MCP-1 ELISA; macrophage migration assay Journal of cellular physiology Medium 24420912
2014 MCP-1 promotes invasion and adhesion of human ovarian cancer (SKOV-3) cells via CCR2; CCR2 antagonist blocked MCP-1-induced invasion and adhesion, and CCR2 expression was confirmed in SKOV-3 cells. Transwell invasion assay; cell adhesion assay; CCR2 antagonist treatment; immunohistochemistry for CCR2 Anticancer research Low 24222114
2014 MCP-1 stimulates spinal microglia via the PI3K/Akt pathway in bone cancer pain; intrathecal anti-MCP-1 antibody or PI3K inhibitor LY294002 reduced p-Akt and OX-42 expression in spinal dorsal horns, and LY294002 attenuated mechanical allodynia. Bone cancer pain rat model; in vitro microglia stimulation with recombinant MCP-1; Western blot for p-Akt and OX-42; pharmacological PI3K inhibitor; intrathecal anti-MCP-1 neutralizing antibody; behavioral pain testing Brain research Medium 25555372
2018 MCP-1 drives triple-negative breast cancer cell invasion via the CCR2 receptor and MAP kinase (MEK/ERK) pathway; CCR2 antagonist and MEK inhibitor U0126 both blocked MCP-1-induced invasion; MCP-1 knockdown in BT-549 cells decreased invasion and downregulated EMT markers N-cadherin and vimentin. Boyden chamber invasion assay; CCR2 antagonist; MEK inhibitor U0126; siRNA knockdown of MCP-1; qRT-PCR and ELISA for MCP-1; Western blot for EMT markers Breast cancer research and treatment Medium 29594759
2018 MCP-1/CCR2 signaling mediates ethanol-induced microglial activation/neuroinflammation and neuroapoptosis in the developing brain; MCP-1-KO and CCR2-KO mice were more resistant to ethanol-induced neuroapoptosis; MCP-1 inhibitor (Bindarit) and CCR2 antagonist (RS504393) reduced neuroinflammation; mechanistically, blocking MCP-1/CCR2 attenuated ethanol-induced activation of TLR4 and GSK3β. MCP-1-KO and CCR2-KO mice; ethanol neonatal exposure model; immunohistochemistry and immunoblotting; neuron/microglia co-culture; pharmacological inhibitors Bindarit and RS504393; TLR4 and GSK3β signaling analysis Journal of neuroinflammation High 29976212
2019 I/R-induced MCP-1 release regulates cardiomyocyte apoptosis via CaSR (Ca2+-sensing receptor) acting as upstream effector of MCPIP1 (MCP-1-induced protein 1), which in turn activates ER stress but not autophagy; CCR2 inhibitor RS-102895 and CaSR inhibitor NPS-2143 both reduced I/R-induced apoptosis. HL-1 cardiac cells and primary neonatal cardiomyocytes; simulated I/R; CCR2 inhibitor (RS-102895); CaSR inhibitor (NPS-2143) and activator (evocalcet); Hoechst staining and flow cytometry apoptosis; ER stress markers by Western blot; ELISA for MCP-1 American journal of physiology. Heart and circulatory physiology Medium 31774703
2023 In NASH, hepatocyte-specific Notch signaling transactivates the Ccl2 promoter via an evolutionarily conserved Notch/RBPJ binding site, driving hepatocyte-derived MCP-1 secretion that recruits monocyte-derived macrophages and causes liver fibrosis; hepatocyte-specific Ccl2-KO reduced MoMF infiltrate and fibrosis, while forced hepatocyte MCP-1 expression caused the opposite phenotype, and CCR2 inhibitor ameliorated these effects. Hepatocyte-specific Ccl2-KO mice; hepatocyte-specific Notch gain-of-function mice; CCR2 inhibitor treatment; Ccl2 promoter analysis (RBPJ site); NASH diet mouse model; liver histology for fibrosis and macrophage markers JCI insight High 36752206
1996 Lysophosphatidylcholine (LPC) stimulates MCP-1 mRNA expression and protein secretion in human vascular endothelial cells (HUVECs) via protein kinase C (PKC) pathway; PKC inhibitor staurosporine attenuated LPC-induced MCP-1 mRNA increase by 53%. HUVEC cultures; LPC treatment; ELISA for MCP-1 protein; Northern blot/mRNA quantification; staurosporine (PKC inhibitor) co-treatment Metabolism: clinical and experimental Low 8622597
2003 Smad-3 stimulates basal and HIV-1 Tat-mediated MCP-1 transcription in human astrocytic cells, while Smad-4 decreases both Smad-3- and Tat-induced MCP-1 promoter activity; Smad-3 and Smad-4 physically associate with the N-terminal region (residues 1–40) of Tat, and the MH2 domain of Smad-3 is required for this transcriptional cooperation. Transfection reporter assays (MCP-1 promoter-luciferase); protein-binding studies (co-association of Smad domains with Tat); domain deletion/mutation analysis of Smad Virology Medium 12758167
2010 p53 directly binds to a site ~2.5 kb upstream of the MCP-1 transcriptional start site (confirmed by EMSA and ChIP) and is required for TNF-α-induced MCP-1 transcription in keratinocytes; HPV E6-mediated p53 degradation abolishes TNF-α-induced MCP-1 expression, and siRNA against p53 decreased MCP-1 transcription, confirming a p53–MCP-1 transcriptional axis. EMSA (electrophoretic mobility shift assay); chromatin immunoprecipitation (ChIP); siRNA knockdown of p53; HPV E6/E7 expressing cell lines; temperature-sensitive p53 mutant cells; Li-Fraumeni cells Molecular cancer High 20406462
2003 17β-estradiol (E2) inhibits MCP-1 gene expression in keratinocytes through estrogen receptor beta (ERβ), which physically associates (co-immunoprecipitation) with Sp1 or AP-1 in an E2-dependent manner, inhibiting their transcriptional activity at the Sp1 and AP-1 elements in the MCP-1 promoter without blocking their DNA binding. MCP-1 promoter-luciferase reporter; ERβ transfection; estrogen receptor antagonist ICI 182780; Sp1 and AP-1 transcriptional activity assays; co-immunoprecipitation (ERβ with Sp1/AP-1); ERβ domain deletion/mutation analysis The Journal of investigative dermatology High 12787135
2014 Dominant negative MCP-1 (7ND) blocks human osteoclast differentiation by preventing early induction of calmodulin 1 (CALM1), JUN, and NFATc2; MCP-1 mRNA was induced >1000-fold within 24 h of RANKL treatment, preceding induction of NFATc1, NFATc2, cathepsin K, and TRAP, placing MCP-1 induction at the apex of the RANKL-driven osteoclastogenesis cascade. Human cord blood CFU-GM differentiation to osteoclasts; quantitative PCR for multiple osteoclast markers over time course; dominant negative MCP-1 (7ND) treatment; temporal gene expression profiling Journal of cellular biochemistry Medium 23996571
2021 Adiponectin suppresses TNF-α-stimulated MCP-1 expression in hepatocytes via the APPL2-mTORC1 signaling axis; hepatocyte-specific APPL2 knockout enhanced adiponectin sensitivity, blocked TNF-α-induced MCP-1 expression, and reduced macrophage infiltration and hepatic inflammation, while concomitant adiponectin knockout reversed these effects. Hepatocyte-specific APPL2 KO mice; adiponectin KO mice; double KO strategy; high-fat diet model; mTORC1 signaling analysis; macrophage infiltration histology; MCP-1 ELISA Diabetes High 34162682
2006 High-glucose/hyperosmolarity-induced MCP-1 expression in peritoneal mesothelial cells is mediated by PKC activation and downstream NF-κB (not by MEK/ERK, p38 MAPK, or JNK); prednisolone inhibited NF-κB DNA binding and MCP-1 expression by increasing IκBα, and this effect was reversed by a glucocorticoid receptor antagonist. Rat peritoneal mesothelial cells; high-glucose/mannitol treatment; pharmacological inhibitors of PKC, NF-κB, MEK, p38, JNK; EMSA for NF-κB binding; Western blot; MCP-1 RT-PCR and ELISA; glucocorticoid receptor antagonist mifepristone Kidney international Medium 16518329

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Monocyte chemoattractant protein-1 (MCP-1): an overview. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 3078 19441883
1999 MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1013 10227295
2021 MCP-1: Function, regulation, and involvement in disease. International immunopharmacology 702 34233864
1990 Human monocyte chemoattractant protein-1 (MCP-1). Immunology today 580 2186747
2007 Increased MCP-1 and microglia in various regions of the human alcoholic brain. Experimental neurology 428 18190912
2010 MCP-1: chemoattractant with a role beyond immunity: a review. Clinica chimica acta; international journal of clinical chemistry 385 20633546
2003 The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Seminars in immunology 353 12495638
2010 The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. Journal of neuroimmunology 340 20681057
2012 Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes. Cytokine 314 22766373
2001 Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. The American journal of pathology 262 11485904
1996 Increased MCP-1, RANTES, and MIP-1alpha in bronchoalveolar lavage fluid of allergic asthmatic patients. American journal of respiratory and critical care medicine 257 8616572
2002 Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Diabetes 245 11756323
2009 Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clinical science (London, England : 1979) 242 19566488
2003 MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis. Journal of neurochemistry 242 12753088
2018 The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cellular & molecular immunology 227 29375123
2001 MCP-1 and RANTES are mediators of acute and chronic inflammation. Allergy and asthma proceedings 219 11424873
2003 Significant involvement of CCL2 (MCP-1) in inflammatory disorders of the lung. Microcirculation (New York, N.Y. : 1994) 209 12851645
1997 MCP-1 protects mice in lethal endotoxemia. The Journal of clinical investigation 208 9185504
2006 The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney international 178 16609683
1997 Release of RANTES, MIP-1 alpha, and MCP-1 into asthmatic airways following endobronchial allergen challenge. American journal of respiratory and critical care medicine 165 9372648
2011 CCL2/MCP-1 modulation of microglial activation and proliferation. Journal of neuroinflammation 159 21729288
2007 Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice. Journal of the American Society of Nephrology : JASN 153 17625118
2014 Impact of MCP-1 in atherosclerosis. Current pharmaceutical design 144 24862889
1999 Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney international 141 10469372
2009 Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. The Journal of neuroscience : the official journal of the Society for Neuroscience 124 19129402
2000 MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy. Kidney international 124 10886563
2010 MCP-1 gene activation marks acute kidney injury. Journal of the American Society of Nephrology : JASN 121 21071523
2002 Oxalate ions and calcium oxalate crystals stimulate MCP-1 expression by renal epithelial cells. Kidney international 119 11786090
1999 Increased MCP-1 and MIP-1beta in bronchoalveolar lavage fluid of chronic bronchitics. The European respiratory journal 118 10489845
1999 MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis. Kidney international 117 10469367
1998 Estradiol suppresses MCP-1 expression In vivo : implications for atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 114 9763529
2002 MCP-1 causes leukocyte recruitment and subsequently endotoxemic ileus in rat. American journal of physiology. Gastrointestinal and liver physiology 106 11751168
2001 Neuronal MCP-1 expression in response to remote nerve injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 101 11149670
2018 MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis. Breast cancer research and treatment 90 29594759
2021 The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases. Journal of cellular physiology 89 33782965
2008 Role of MCP-1 in endotoxemia and sepsis. International immunopharmacology 87 18442784
2002 MCP-1 expression in endotoxin-induced uveitis. Investigative ophthalmology & visual science 87 11980865
2013 MCP-1 binds to oxidized LDL and is carried by lipoprotein(a) in human plasma. Journal of lipid research 86 23667177
1997 Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis. Journal of leukocyte biology 85 9365123
2013 IκBζ is a transcriptional key regulator of CCL2/MCP-1. Journal of immunology (Baltimore, Md. : 1950) 84 23547114
2018 Role of MCP-1 and CCR2 in ethanol-induced neuroinflammation and neurodegeneration in the developing brain. Journal of neuroinflammation 83 29976212
2016 Aging and serum MCP-1 are associated with gut microbiome composition in a murine model. PeerJ 83 27069796
2010 MCP-1 contributes to arteriovenous fistula failure. Journal of the American Society of Nephrology : JASN 83 21115617
2004 Essential role for Smad3 in regulating MCP-1 expression and vascular inflammation. Circulation research 82 14752027
2000 Increased expression of chemokines (MCP-1, MIP-1alpha, RANTES) after peripheral nerve transection. Journal of the peripheral nervous system : JPNS 82 10905466
2007 MCP-1/CCL2 as a therapeutic target in myocardial infarction and ischemic cardiomyopathy. Inflammation & allergy drug targets 80 17692033
2009 MCP-1 expressed by osteoclasts stimulates osteoclastogenesis in an autocrine/paracrine manner. Biochemical and biophysical research communications 79 19364494
1998 Synergistic induction of MCP-1 and -2 by IL-1beta and interferons in fibroblasts and epithelial cells. Journal of leukocyte biology 73 9500525
2014 Exosomal ATF3 RNA attenuates pro-inflammatory gene MCP-1 transcription in renal ischemia-reperfusion. Journal of cellular physiology 71 24420912
2003 Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells. Journal of neuroimmunology 70 14512159
1996 Lysophosphatidylcholine stimulates the expression and production of MCP-1 by human vascular endothelial cells. Metabolism: clinical and experimental 70 8622597
2023 Notch-mediated hepatocyte MCP-1 secretion causes liver fibrosis. JCI insight 68 36752206
2008 Role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages. American journal of physiology. Heart and circulatory physiology 68 18296557
2024 Role of MCP-1 as an inflammatory biomarker in nephropathy. Frontiers in immunology 66 38239353
2012 MCP-1 induced protein promotes adipogenesis via oxidative stress, endoplasmic reticulum stress and autophagy. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 66 22739135
2018 Role of MCP-1 and CCR2 in alcohol neurotoxicity. Pharmacological research 61 30472461
2010 Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization. Biomaterials 61 20110124
2010 Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases. Brain, behavior, and immunity 61 20193755
2017 ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR-124 upregulation. Oncotarget 58 29340098
2013 MCP-1 promotes invasion and adhesion of human ovarian cancer cells. Anticancer research 57 24222114
2008 Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathway. Glia 56 18383340
2005 MCP-1/CCL2 protects cardiac myocytes from hypoxia-induced apoptosis by a G(alphai)-independent pathway. Biochemical and biophysical research communications 56 16102724
1997 MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression. Journal of leukocyte biology 55 9225989
2014 The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation. Biomaterials 54 24881026
2010 Regulation of MCP-1 chemokine transcription by p53. Molecular cancer 53 20406462
2002 MCP-1 expression in CNS-1 astrocytoma cells: implications for macrophage infiltration into tumors in vivo. Journal of neuro-oncology 51 11949821
2006 MCP-1 parallels inflammatory and regenerative responses in ischemic muscle. The Journal of surgical research 50 16488443
2011 Endogenous MCP-1 promotes lung inflammation induced by LPS and LTA. Molecular immunology 49 21529952
2017 Urinary MCP-1 as a biomarker for lupus nephritis: a meta-analysis. Zeitschrift fur Rheumatologie 48 27278779
2014 MCP-1 stimulates spinal microglia via PI3K/Akt pathway in bone cancer pain. Brain research 48 25555372
2011 MCP-1 and IL-8 as pain biomarkers in fibromyalgia: a pilot study. Pain medicine (Malden, Mass.) 46 21714842
2007 MCP-1 targeting inhibits muscularis macrophage recruitment and intestinal smooth muscle dysfunction in colonic inflammation. American journal of physiology. Cell physiology 45 17977946
2003 17Beta-estradiol inhibits MCP-1 production in human keratinocytes. The Journal of investigative dermatology 45 12787135
1991 Biological aspects of monocyte chemoattractant protein-1 (MCP-1). Advances in experimental medicine and biology 45 1755379
2021 Urinary EGF and MCP-1 and risk of CKD after cardiac surgery. JCI insight 44 33974569
2004 Adult porcine islets produce MCP-1 and recruit human monocytes in vitro. Xenotransplantation 44 14962280
2009 Soy phosphatidylcholine inhibited TLR4-mediated MCP-1 expression in vascular cells. Atherosclerosis 43 19215923
2002 Expression of the chemokines MCP-1/CCL2 and RANTES/CCL5 is differentially regulated by infiltrating inflammatory cells. Kidney international 43 12234296
2012 RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis. Molecular immunology 42 22750227
2010 Impact of RANTES, MCP-1 and IL-8 in mast cells. Journal of biological regulators and homeostatic agents 41 20385066
2003 Regulation of MCP-1 gene transcription by Smads and HIV-1 Tat in human glial cells. Virology 40 12758167
2021 Adiponectin Alleviates Diet-Induced Inflammation in the Liver by Suppressing MCP-1 Expression and Macrophage Infiltration. Diabetes 38 34162682
2020 Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis. Frontiers in immunology 38 32218781
2015 Role of MCP-1 in alcohol-induced aggressiveness of colorectal cancer cells. Molecular carcinogenesis 38 26014148
2013 MCP-1 in psoriatic patients: effect of biological therapy. The Journal of dermatological treatment 38 23480385
2021 MCP-1 targeting: Shutting off an engine for tumor development. Oncology letters 37 34868363
2019 MCP-1 deficiency enhances browning of adipose tissue via increased M2 polarization. The Journal of endocrinology 36 31137011
2018 MCP-1, KC-like and IL-8 as critical mediators of pathogenesis caused by Babesia canis. PloS one 36 29304171
2003 Protein kinase C beta is required for human monocyte chemotaxis to MCP-1. The Journal of biological chemistry 36 12724308
1999 Regulated expression of MCP-1 by osteoblastic cells in vitro and in vivo. Histology and histopathology 36 10506949
2010 Plasma levels of MCP-1 and adiponectin in obstructive sleep apnea syndrome. Archives of otolaryngology--head & neck surgery 35 20855682
2005 MCP-1 gene (SCYA2) and schizophrenia: a case-control association study. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 35 15389752
2021 MCP-1 Predicts Recurrent Cardiovascular Events in Patients with Persistent Inflammation. Journal of clinical medicine 34 33803115
2019 MCP-1 mediates ischemia-reperfusion-induced cardiomyocyte apoptosis via MCPIP1 and CaSR. American journal of physiology. Heart and circulatory physiology 34 31774703
2010 MCP-1 promotes mural cell recruitment during angiogenesis in the aortic ring model. Angiogenesis 34 20571857
2014 Dominant negative MCP-1 blocks human osteoclast differentiation. Journal of cellular biochemistry 33 23996571
2010 Suppressor of cytokine signaling-1 ameliorates expression of MCP-1 in diabetic nephropathy. American journal of nephrology 32 20299783
2006 Prednisolone inhibits hyperosmolarity-induced expression of MCP-1 via NF-kappaB in peritoneal mesothelial cells. Kidney international 32 16518329
2010 Regulation of MCP-1 production in brain by stress and noradrenaline-modulating drugs. Journal of neurochemistry 31 20132473
2000 Monocyte chemoattractant protein 1 (MCP-1) in temporal arteritis and polymyalgia rheumatica. Annals of the rheumatic diseases 29 11005777

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