Affinage

CXCL2

C-X-C motif chemokine 2 · UniProt P19875

Length
107 aa
Mass
11.4 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 40 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

CXCL2 is a secreted CXC chemokine that functions as a potent neutrophil chemoattractant, acting through the receptor CXCR2 to direct innate immune cell trafficking and to amplify inflammation (PMID:23645836, PMID:23433011). It is produced by mast cells (preformed in granules and newly synthesized via TLR4), tissue macrophages, neutrophils, fibroblasts, microglia, and other cell types, and these distinct sources stage sequential and self-amplifying waves of neutrophil recruitment (PMID:23645836, PMID:31852751). Neutrophil-derived CXCL2 establishes an autocrine/paracrine positive-feedback loop that amplifies its own production and enhances antibacterial functions including oxygen radical release (PMID:31852751, PMID:26802238, PMID:30012158). During transmigration, CXCL2 deposited by migrating neutrophils is captured by the atypical chemokine receptor ACKR1 at endothelial junctions to create a chemokine depot that drives unidirectional luminal-to-abluminal migration, a role functionally distinct from CXCL1 (PMID:30446388). CXCL2 exists as monomers, homodimers, and Cxcl1-Cxcl2 heterodimers with distinct CXCR2 potencies and heparan-sulfate affinities, and neutrophil recruitment is determined by the combined interplay of receptor activation and domain-specific glycosaminoglycan binding rather than either alone (PMID:32881070, PMID:37625009, PMID:30248108). Through CXCR2, CXCL2 couples to G-protein and β-arrestin pathways and engages downstream PKC/MAPK, integrin-linked kinase, and NLRP3 inflammasome signaling in diverse contexts (PMID:32881070, PMID:28739876). CXCL2 transcription is driven by NF-κB together with STAT1, AP-1/c-Jun, c-Fos, Fli-1, and NFATc3 acting on defined promoter elements, and is restrained by regulators including PXR, SIRT2/MKP-1, and IFNγ (PMID:24280128, PMID:27889620, PMID:22379036, PMID:21507677, PMID:37523510, PMID:33076328, PMID:25349202, PMID:30012158). Beyond immunity, CXCL2 drives osteoclastogenesis by upregulating stromal RANKL and inhibits osteoblast differentiation through ERK1/2 suppression (PMID:22771802, PMID:31292171), and is degraded extracellularly by the secreted protease PRSS35 at a tandem lysine motif to limit neutrophil recruitment and NET formation (PMID:36934105).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2004 Medium

    Establishing where CXCL2 is constitutively made was needed to distinguish baseline from inflammation-induced expression; mapping it to a defined bone marrow granulocyte subset showed CXCL2 production is cell-type-restricted and not simply inducible.

    Evidence RT-PCR and intracellular FACS with surface marker co-staining across mouse tissues

    PMID:15466452

    Open questions at the time
    • Does not define the functional role of constitutive CXCL2 in the marrow granulocyte subset
    • No mechanism for tissue-restricted expression pattern
  2. 2008 Medium

    Linking CXCL2 induction to specific upstream signaling resolved how pathogen and danger stimuli converge on the gene; p38 MAPK-IKK-NF-κB and P2X7-driven NFAT/PKC-MAPK pathways were shown to drive CXCL2 transcription in dendritic cells and microglia.

    Evidence Pharmacological inhibitors, siRNA, NF-κB KO mice, reporter and chemotaxis assays

    PMID:18985311 PMID:20477948

    Open questions at the time
    • Single-lab, single-stimulus contexts
    • Relative contribution of parallel pathways not quantified in vivo
  3. 2011 High

    Demonstrating direct recruitment of c-Fos and p65 to the CXCL2 promoter and linking macrophage CXCL2 to bone destruction connected transcriptional control to a pathological osteoclast phenotype.

    Evidence ChIP, signaling inhibitors, neutralizing antibodies, in vivo bone destruction model, osteoclastogenesis assays

    PMID:21507677

    Open questions at the time
    • ROS requirement for secretion vs mRNA not mechanistically resolved
    • Promoter occupancy kinetics not addressed
  4. 2013 High

    Defining the cellular choreography of CXCL2 release answered how recruitment is initiated and sustained: mast cell granules and macrophages provide sequential CXCL1/CXCL2 sources, and microbial/IL-1β stimuli engage NF-κB/STAT1 in tissue cells.

    Evidence Mast cell-deficient and macrophage-depleted mice, neutralizing antibodies, intravital microscopy, promoter mutagenesis, ChIP, germ-free and MyD88-KO mice

    PMID:23433011 PMID:23645836 PMID:24280128

    Open questions at the time
    • CXCL1 vs CXCL2 functional non-redundancy not fully dissected
    • Promoter findings tied to specific cell types only
  5. 2018 High

    Resolving CXCL2's spatial role in transmigration showed it is not merely a soluble gradient: ACKR1 captures neutrophil-derived CXCL2 at endothelial junctions to enforce directional migration, distinguishing it from CXCL1.

    Evidence Confocal intravital microscopy, cell-specific knockout mice, neutralizing antibodies

    PMID:30446388

    Open questions at the time
    • Structural basis of ACKR1-CXCL2 presentation not defined
    • How the depot is released to abluminal side unresolved
  6. 2018 High

    Characterizing the biophysical interplay of receptor and matrix binding answered why monomer/dimer/heterodimer forms differ functionally; CXCL2 oligomeric state and domain-specific heparan sulfate binding jointly set recruitment potency.

    Evidence Competition ELISA with anti-HS antibodies, CXCR2 G-protein/β-arrestin assays, HS binding assays, in vivo recruitment

    PMID:30248108 PMID:32881070

    Open questions at the time
    • Structural map of distinct HS-binding domains incomplete
    • In vivo oligomeric equilibrium not directly measured
  7. 2019 High

    Identifying neutrophil endosomal TLR/UNC93B1 control of CXCL2 and the IFNγ brake explained how the CXCL2 autocrine loop is selectively triggered and spatially constrained during infection and CNS inflammation.

    Evidence UNC93B1-deficient and TLR7/9/13 triple-KO mice, IFNγR-KO mice, BM chimeras, in vitro/in vivo stimulation

    PMID:30012158 PMID:31852751

    Open questions at the time
    • Selectivity for CXCL2 over CXCL1 mechanism incomplete
    • Endosomal signaling-to-promoter link not fully traced
  8. 2023 High

    Defining the Cxcl1-Cxcl2 heterodimer as the most potent recruiter and identifying PRSS35 as an extracellular protease established both a gain-of-function ligand species and a post-secretion off-switch for CXCL2.

    Evidence In vivo neutrophil recruitment, GAG binding/CXCR2 assays, in vitro cleavage reconstitution with motif mutagenesis, proprotein convertase assays, tumor models

    PMID:36934105 PMID:37625009

    Open questions at the time
    • Structural basis of heterodimer-CXCR2 dampening not solved
    • Physiological abundance and regulation of PRSS35-mediated turnover unquantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CXCL2 oligomeric state, GAG presentation, ACKR1 depots, and extracellular proteolysis are integrated in vivo to set the magnitude and spatial precision of neutrophil recruitment remains unresolved.
  • No unified structural/quantitative model linking ligand form to receptor signaling output
  • Direct in vivo measurement of CXCL2 monomer/dimer/heterodimer ratios lacking
  • Generality of PRSS35 turnover across tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 2
Partners
ACKR1CXCR2PRSS35

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 CXCL2 produced by transmigrating neutrophils is presented by the atypical chemokine receptor ACKR1 (enriched within endothelial junctions) to create a junctional chemokine 'depot' that enables efficient unidirectional luminal-to-abluminal neutrophil migration through venular walls, distinct from CXCL1 which guides luminal and sub-endothelial crawling. Confocal intravital microscopy, genetic mouse models (cell-specific knockouts), neutralizing antibodies Immunity High 30446388
2013 CXCL2 (along with CXCL1) is released by mast cell granules (preformed) and newly synthesized via TLR4-dependent signaling; mast cells initiate early neutrophil recruitment and tissue macrophages sustain further neutrophil penetration, both through CXCL1/CXCL2-dependent chemotaxis shown by blocking monoclonal antibodies in vivo and in vitro chemotaxis assays. Mast cell-deficient mice, clodronate macrophage depletion, in vivo neutralizing antibodies, in vitro chemotaxis assays, intravital microscopy Blood High 23645836
2013 IL-1β-induced transcription of CXCL1 and CXCL2 genes in pancreatic β-cells requires NF-κB (p65/p50 subunits binding to consensus κB elements in both promoters) and serine-phosphorylated STAT1, with accompanying histone H3 modifications and increased RNA polymerase II phosphorylation. Promoter mutation analysis, ChIP assay, siRNA knockdown, reporter assays, Western blot American journal of physiology. Endocrinology and metabolism High 24280128
2010 P2X7 receptor activation induces CXCL2 production in microglia through two parallel signaling pathways: NFAT activation and protein kinase C/MAPK (p38, ERK, JNK) pathways; PKC inhibitors suppressed ERK/JNK activation and CXCL2 expression, while MAPK inhibitors did not block NFAT activation. P2X7R agonist/antagonist pharmacology, NFAT inhibitor, MAPK inhibitors, PKC inhibitors, qPCR, ELISA Journal of neurochemistry Medium 20477948
2016 Fli-1 (an Ets transcription factor) directly binds the CXCL2 promoter (shown by ChIP) and drives CXCL2 transcription in a dose-dependent manner in endothelial cells; Fli-1 siRNA knockdown reduces LPS/TNF-α-stimulated CXCL2 production, and Fli-1 acts additively with NF-κB p65 on CXCL2 promoter activation. ChIP assay, siRNA knockdown, transient transfection/reporter assay, ELISA Molecular immunology High 27889620
2014 SIRT2 positively regulates LPS-induced CXCL2 expression in renal tubular cells: SIRT2 interacts with MKP-1 (MAPK phosphatase-1), and SIRT2 knockdown increases MKP-1 acetylation, suppresses p38 MAPK and JNK phosphorylation, and reduces p65 binding to the CXCL2 promoter, thereby decreasing CXCL2 production. Sirt2-/- mice, siRNA knockdown, adenoviral overexpression, co-immunoprecipitation, ChIP, Western blot Journal of the American Society of Nephrology : JASN High 25349202
2008 C. difficile toxin A induces CXCL2 expression in dendritic cells via p38 MAPK-dependent activation of IKK and NF-κB (p65/p50 heterodimers); p38 inhibition (SB203580 or siRNA) significantly reduced IKK activity, DC maturation, and CXCL2 upregulation, and NF-κB KO mice showed reduced CXCL2 expression and neutrophil chemoattraction. Pharmacological inhibitors, siRNA, NF-κB knockout mice, reporter assay, ELISA, chemotaxis assay Journal of molecular medicine (Berlin, Germany) Medium 18985311
2011 LPS induces CXCL2 transcription in bone marrow macrophages via p38, JNK, and NF-κB signaling pathways; c-Fos and p65 are directly recruited to the CXCL2 promoter (by ChIP); reactive oxygen species are required for CXCL2 secretion but not mRNA expression; CXCL2 from LPS-treated macrophages promotes osteoclast precursor migration and osteoclastogenesis, and CXCL2 neutralization prevents LPS-induced bone destruction in vivo. ChIP assay, signaling inhibitors, neutralizing antibodies, in vivo mouse model, osteoclastogenesis assay Cytokine High 21507677
2017 CXCL1/CXCL2 acting through CXCR2 activates NLRP3 inflammasome in macrophages via a PKCμ-dependent integrin-linked kinase (ILK) pathway; siRNA knockdown or pharmacological inhibition of ILK or PKCμ compromised inflammasome activation and bioactive IL-1β production; in vivo CXCL1/CXCL2 blockade reduced M. tuberculosis-induced IL-1β. siRNA knockdown, pharmacological inhibitors, in vivo antibody blockade, in vivo mouse models Journal of immunology (Baltimore, Md. : 1950) Medium 28739876
2020 Cxcl2 exists as monomers and dimers and signals through Cxcr2 via both G-protein and β-arrestin pathways; Cxcl2 variants showed higher Cxcr2 potency compared to Cxcl1 variants; native Cxcl1 bound heparan sulfate (HS) with higher affinity than native Cxcl2, but dimers bound HS with higher affinity than native proteins; peritoneal neutrophil recruitment is determined by complex interplay of Cxcr2 activation and GAG binding rather than either alone. Cellular CXCR2 G-protein and β-arrestin activity assays, HS binding assays, in vivo peritoneal recruitment, flow cytometry Journal of leukocyte biology High 32881070
2023 The Cxcl1-Cxcl2 heterodimer is more potent at neutrophil recruitment than either individual chemokine; the heterodimer binds glycosaminoglycans with higher affinity than Cxcl1 or Cxcl2 alone and shows dampened CXCR2 receptor activity relative to its strong recruitment activity, suggesting optimal GAG interactions combined with dampened receptor desensitization promote robust recruitment. In vivo peritoneal neutrophil recruitment, CXCR2 cellular activity assays, GAG binding assays, flow cytometry Journal of leukocyte biology Medium 37625009
2008 CXCL2 (MIP-2) acting on CXCR2 induces dose-dependent neurotoxicity in primary rat motor neurons; this toxicity is abrogated by the CXCR1/2 inhibitor reparixin and is absent in motor neurons from CXCR2-deficient mice, demonstrating direct CXCR2-dependent motor neuron death. Primary motor neuron cultures, pharmacological inhibition (reparixin), CXCR2 knockout mouse neurons, immunocytochemistry Neuroimmunomodulation High 18391506
2016 IC-activated neutrophils express high levels of CXCL2, which amplifies neutrophil recruitment and activation in an autocrine/paracrine manner; neutralization of CXCL2 (but not CXCL1) in the interstitium effectively reduced neutrophil recruitment, establishing a CXCL2-driven positive-feedback loop distinct from tissue-resident cell-derived CXCL1. Multiphoton intravital microscopy, in vivo neutralizing antibodies, genomic approaches The Journal of investigative dermatology Medium 26802238
2019 Neutrophils produce Cxcl2 (but not Cxcl1) in response to bacteria (GBS and other species) via multiple endosomal TLRs requiring UNC93B1 chaperone; simultaneous absence of TLR7, 9, and 13 recapitulates UNC93B1-defective phenotype; neutrophil-derived Cxcl2 acts autocrinously to amplify its own production and enhance antibacterial activities including oxygen radical release. Cell depletion experiments, UNC93B1-deficient mice, TLR7/9/13 triple KO mice, in vitro stimulation, in vivo peritonitis model Journal of immunology (Baltimore, Md. : 1950) High 31852751
2012 CXCL2 produced by rotavirus-infected hepatic macrophages (not cholangiocytes) is the essential mediator of neutrophil chemotaxis; anti-Mip2/Cxcl2 antibodies completely prevented neutrophil chemotaxis induced by conditioned media from infected macrophages. In vitro infection of cell lines, conditioned media chemotaxis assay, neutralizing antibody depletion, PCR, ELISA, immunostaining Pediatric research Medium 20234283
2020 Pregnane X receptor (PXR) suppresses CXCL2 transcription through both NF-κB and AP-1 binding sites in the Cxcl2 promoter; mutation of both NF-κB and AP-1 sites abolished PXR-dependent suppression in reporter assays; PXR agonist treatment in vivo reduced hepatic Cxcl2 expression and neutrophil infiltration. Reporter assays with wild-type and mutated Cxcl2 promoter, in vivo mouse treatment, qRT-PCR Cells Medium 33076328
2012 ERK2-dependent activation of c-Jun is required for NTHi-induced CXCL2 upregulation in inner ear spiral ligament fibrocytes; two AP-1 motifs in the CXCL2 5'-flanking region serve as NTHi-responsive elements, with the proximal AP-1 motif showing higher binding affinity for NTHi-activated c-Jun; CXCL2 release from fibrocytes recruits polymorphonuclear cells to the cochlea. MEK1/ERK2 inhibition, c-Jun knockdown, promoter binding analysis, chemotaxis assay Journal of immunology (Baltimore, Md. : 1950) Medium 22379036
2014 Daidzein suppresses TNF-α-induced Cxcl2 transcription in murine lung epithelial cells by inhibiting PARP-1 activity, which reduces RelA/p65 protein PARylation required for NF-κB-driven Cxcl2 promoter activation; PARP-1 overexpression enhanced Cxcl2 promoter activity which was blocked by daidzein. Reporter assays (NF-κB-luc, Cxcl2-luc), PARP-1 expression plasmid transfection, Western blot/immunoprecipitation for PARylation, PARP-1 activity assay, in vivo mouse model Acta pharmacologica Sinica Medium 24632845
2021 A nucleus-localized lncRNA (lnc-Cxcl2) transcribed from the Cxcl2 gene locus acts in cis to inhibit Cxcl2 transcription in mouse lung epithelial cells by binding to the Cxcl2 promoter and recruiting ribonucleoprotein La, which inhibits chromatin accessibility; lnc-Cxcl2-deficient mice show increased Cxcl2 expression and more severe lung inflammation after influenza infection. (NOTE: This finding is about the lncRNA product, not the CXCL2 protein itself.) lnc-Cxcl2-deficient mice, chromatin accessibility assays, promoter binding analysis, RNA immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America Low 34607953
2023 The secreted pseudo-serine protease PRSS35 suppresses CXCL2 protein levels through targeted proteolytic cleavage of a tandem lysine (KK) recognition motif on CXCL2; PRSS35 is processed by proprotein convertases to generate its active form; CXCL2 degradation by PRSS35 attenuates neutrophil recruitment and NET formation in HCC. In vitro protease cleavage assay, site-directed mutagenesis of cleavage motif, proprotein convertase assays, in vivo tumor models, immunoprecipitation Nature communications High 36934105
2021 Macrophage-derived extracellular vesicles carry CXCL2 on their surface, which recruits neutrophils in vitro and in vivo; CXCL2 on macrophage EVs activates the CXCR2/PKC/NOX4 signaling pathway in neutrophils to induce tissue damage. EV isolation, CXCL2 knockdown in macrophages, in vitro neutrophil chemotaxis, in vivo sepsis model, Western blot Journal of immunology (Baltimore, Md. : 1950) Medium 34507947
2018 CXCL2-CXCR2 axis in CPT-11-resistant colon cancer cells signals through Gαi-2 and Gαq/11 G-proteins to promote cancer stem cell properties (CSC markers, EMT markers, MMPs); CXCL2 shRNA knockdown reduced CSC protein expression, cyclins, EMT markers, G-protein levels, and MMP expression. shRNA knockdown, double immunofluorescence, Western blot, colony-formation assay Journal of cellular physiology Medium 30552676
2015 Bone marrow adipocyte-conditioned media is a significant source of CXCL1 and CXCL2; both recombinant CXCL1 and CXCL2 accelerate osteoclast maturation via CXCR2 signaling, an effect blockable by neutralizing antibodies to either chemokine or by CXCR2 antagonist. In vitro osteoclastogenesis assay, adipocyte-conditioned media, neutralizing antibodies, CXCR2 antagonist, in vivo diet-induced adiposity models Clinical & experimental metastasis Medium 25802102
2012 CXCL2 synthesized by oral squamous cell carcinoma cells promotes osteoclastic bone resorption by upregulating RANKL expression in stromal cells; anti-human CXCL2 neutralizing antibody dose-dependently blocked osteoclast induction by cancer cell-conditioned medium; recombinant CXCL2 directly increased RANKL expression in UAMS-32 stromal cells. Co-culture osteoclastogenesis assay, neutralizing antibody, recombinant CXCL2 treatment, in vivo xenograft model, microarray, immunohistochemistry Biochemical and biophysical research communications Medium 22771802
2019 CXCL2 inhibits osteoblast differentiation through inhibition of the ERK1/2 MAPK signaling pathway; ERK1/2 activation abolishes the inhibitory effect of CXCL2 on osteoblasts, while ERK1/2 inactivation reverses the pro-osteogenic effect of CXCL2 inhibition; CXCL2 neutralization in bone marrow alleviates bone loss in vivo. CXCL2 overexpression/knockdown in osteoblasts, ERK1/2 pharmacological activation/inhibition, in vivo antibody neutralization, Western blot, differentiation assays Journal of cell science Medium 31292171
2020 CXCL2-CXCR2 signaling mediates colon cancer cell adhesion to ECM proteins (vitronectin, fibronectin, fibrinogen) via αV integrin in a CXCR2-dependent manner; immunoneutralization of αV integrin abolished CXCL2-triggered adhesion and inhibited peritoneal metastasis by 69% in vivo; CXCR2 antagonist reduced metastatic nodules by 70%. In vitro migration/proliferation assays, ECM adhesion assay, integrin subunit antibody blockade, in vivo peritoneal metastasis mouse model, CXCR2 antagonist (SB225002) Clinical & experimental metastasis Medium 34115261
2015 Pressure force-induced CXCL2 and CCL2 expression in osteoblasts requires the IL-1β-MyD88 signaling axis; MyD88-/- osteoblasts fail to upregulate CXCL2 after pressure force; anti-IL-1β antibody impairs pressure-induced CXCL2 mRNA increases and MAP kinase phosphorylation in wild-type but not MyD88-/- osteoblasts. MyD88-/- primary osteoblasts, neutralizing anti-IL-1β antibody, recombinant IL-1β stimulation, MAP kinase phosphorylation assay, qRT-PCR Bone Medium 25603464
2004 Constitutive CXCL2/MIP-2 expression in normal mice is restricted to bone marrow and specifically to a Gr-1high, CD11b+, CD62Lhigh, CXCR2+ granulocyte subset (4-6% of total BM cells); in vitro BM stimulation does not increase the number of CXCL2-positive granulocytes; constitutive CXCL2 and CXCL1/KC expression patterns are tissue-specific and non-overlapping. RT-PCR, FACS analysis with intracellular staining, in vitro BM stimulation International immunology Medium 15466452
2013 Commensal bacteria selectively upregulate CXCL2 (but not CXCL1) in periodontal tissue in a MyD88-dependent manner, increasing neutrophil recruitment; neutrophil recruitment to gingival tissue is entirely CXCR2-dependent; germ-free mice show reduced CXCL2 but intact CXCL1 expression. Germ-free mice, CXCR2-KO mice, MyD88-KO mice, quantitative analysis of neutrophils and chemokines in gingival tissue Cellular microbiology Medium 23433011
2018 IFNγ directly suppresses CXCL2 transcription in microglia and CNS-infiltrating myeloid cells, and suppresses CXCR2 transcription in CNS-infiltrating neutrophils; CXCL2 directly stimulates its own expression in neutrophils (autocrine/paracrine loop) enhanced by IL-1 and suppressed by IFNγ, determining anatomical location of CNS inflammatory infiltrates in EAE. IFNγR-KO mice, bone marrow chimeric mice, in vitro cultured neutrophils and macrophages with stimuli, qPCR, flow cytometry, immunohistochemistry, in situ hybridization Journal of neuroinflammation High 30012158
2023 HIF-1α activation (induced by cancer cell-secreted Ref-1) in Schwann cells induces CXCL2 expression; Schwann cell-derived CXCL2 drives macrophage migration via CXCR2; conditional knockdown of CXCL2 in Schwann cells attenuates cancer cell-induced macrophage recruitment and mechanical hypersensitivity in vivo. Co-culture assays, recombinant CXCL2, CXCR2 antagonist, anti-CXCL2 antibody, conditional Schwann cell CXCL2 knockdown, in vivo breast cancer perineural model Brain, behavior, and immunity Medium 36754246
2003 CXCR2 physically associates with AMPA-type glutamate receptors (GluR1) as shown by co-immunoprecipitation in p7 cerebellar granule neurons and in HEK cells co-expressing both receptors; this association inhibits CXCL2-mediated chemotaxis, providing a molecular mechanism for the developmental loss of CXCL2 responsiveness in neurons. Co-immunoprecipitation, chemotaxis assay, CXCR2-expressing HEK cell transfection, primary cerebellar granule neuron cultures Journal of neuroimmunology Medium 12507773
2023 NFATc3 transcription factor regulates CXCL2 gene expression in macrophages; CXCL2 promoter-pGL3 luciferase reporter activity is enhanced by NFATc3 co-transfection; exogenous recombinant CXCL2 restores pulmonary fibrosis phenotype in NFATc3+/- mice, placing CXCL2 downstream of NFATc3 in macrophage-driven fibrosis. NFATc3 KO mice, luciferase reporter assay with NFATc3 co-transfection, adoptive macrophage transfer, in vitro cytokine stimulation, recombinant CXCL2 rescue experiment Aging and disease Medium 37523510
2018 CXCL2 binding to the glomerular endothelial glycocalyx is mediated by heparan sulfate (HS) in a domain-specific manner; CXCL2 and CXCL1 do not compete for the same HS binding sites on glomerular endothelial cells, with differential affinities determined by distinct HS domain structures, shown by competition ELISA with anti-HS scFv antibodies. Competition ELISA with HS preparations and anti-HS scFv antibodies on mouse glomerular endothelial cells (mGEnC-1) PloS one Medium 30248108
2010 CXCL1 (KC) is required upstream of CXCL2 (MIP-2) expression in the lung during Klebsiella pneumoniae infection; KC-/- mice show reduced CXCL2 expression and diminished NF-κB and MAPK activation; in bone marrow-derived and alveolar macrophages, neutralizing KC decreases bacteria-induced MIP-2 production and NF-κB/MAPK activation. KC-/- mice, bone marrow-derived and alveolar macrophage cultures, KC neutralization, NF-κB/MAPK signaling assays Journal of immunology (Baltimore, Md. : 1950) Medium 20937845
2021 CXCL2 overexpression in HCC cells induces apoptosis via both nuclear and mitochondrial apoptosis pathways and negatively regulates the cell cycle via ERK1/2 signaling; CXCL2 overexpression in vivo inhibited subcutaneous tumor growth in nude mice. Lentiviral overexpression, in vitro proliferation/apoptosis assays, ERK1/2 pathway analysis, in vivo xenograft model BMB reports Medium 30293547
2017 TIARP (a six-transmembrane protein) suppresses CXCL2 production by fibroblast-like synoviocytes and reduces CXCR1/CXCR2 expression on neutrophils; TIARP-/- FLS showed enhanced CXCL2 production upon TNF-α stimulation, and TIARP-/- neutrophils showed enhanced CXCL2-driven migration; IL-6R blockade in TIARP-/- mice attenuated arthritis and diminished neutrophil CXCL2-driven recruitment. TIARP-/- mice, DNA microarray, in vitro migration assay, anti-IL-6R antibody treatment, K/BxN serum transfer arthritis model Scientific reports Medium 27995997
2021 CXCL2 secreted by microglia via CXCR2 promotes hippocampal neuronal ferroptosis (elevated MDA, decreased glutathione, iron accumulation, altered ferroptosis protein expression); rmCXCL2 induces microglia self-activation through CXCR2-NF-κB/NLRP3 signaling; CXCR2 antagonist SB225002 reverses CXCL2-induced ferroptosis. Recombinant CXCL2 treatment of neurons, CXCR2 antagonist (SB225002), ferroptosis markers (MDA, GSH, iron, protein levels), NF-κB/NLRP3 signaling assays, in vivo CLP model Phytomedicine Medium 39216299
2015 miR-532-5p directly targets CXCL2 mRNA (validated by luciferase reporter assay) and negatively regulates CXCL2 expression in HCC; CXCL2 promotes HCC cell proliferation and metastasis, and miR-532-5p-mediated inhibition of these phenotypes is reversed by CXCL2 overexpression. Luciferase reporter assay (miR-532-5p target validation), miRNA overexpression/inhibition, cell proliferation and metastasis assays American journal of translational research Medium 26807173
2015 11β-HSD1 in cardiac fibroblasts suppresses CXCL2 (and CXCL5) expression; fibroblast fractions from Hsd11b1-/- hearts show elevated Cxcl2 post-MI; corticosterone or 11-dehydrocorticosterone (11β-HSD1 substrate) provision to cultured cardiac fibroblasts suppresses IL-1α-induced CXCL2 expression; bone marrow chimeras show this effect is attributable to host (non-bone marrow) cells. Hsd11b1-/- mice, bone marrow chimeras, cardiac fibroblast culture with glucocorticoid treatment, gene expression analysis The Journal of endocrinology Medium 28522730

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood 739 23645836
2018 Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis. Immunity 286 30446388
2013 NF-κB and STAT1 control CXCL1 and CXCL2 gene transcription. American journal of physiology. Endocrinology and metabolism 149 24280128
2010 P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways. Journal of neurochemistry 131 20477948
2015 Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer. Clinical & experimental metastasis 130 25802102
2017 CXCL1 and CXCL2 Regulate NLRP3 Inflammasome Activation via G-Protein-Coupled Receptor CXCR2. Journal of immunology (Baltimore, Md. : 1950) 129 28739876
2020 Neutrophil recruitment by chemokines Cxcl1/KC and Cxcl2/MIP2: Role of Cxcr2 activation and glycosaminoglycan interactions. Journal of leukocyte biology 119 32881070
2013 Differential roles of CXCL2 and CXCL3 and their receptors in regulating normal and asthmatic airway smooth muscle cell migration. Journal of immunology (Baltimore, Md. : 1950) 115 23904157
2010 CXCL1 regulates pulmonary host defense to Klebsiella Infection via CXCL2, CXCL5, NF-kappaB, and MAPKs. Journal of immunology (Baltimore, Md. : 1950) 111 20937845
2023 PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway. Signal transduction and targeted therapy 103 36859354
2013 Roles of chemokine ligand-2 (CXCL2) and neutrophils in influencing endothelial cell function and inflammation of human adipose tissue. Endocrinology 95 23372021
2010 Differential expression of the chemokines GRO-2, GRO-3, and interleukin-8 in colon cancer and their impact on metastatic disease and survival. International journal of colorectal disease 94 20162422
2013 Commensal bacteria-dependent select expression of CXCL2 contributes to periodontal tissue homeostasis. Cellular microbiology 93 23433011
2022 SNAIL Induces EMT and Lung Metastasis of Tumours Secreting CXCL2 to Promote the Invasion of M2-Type Immunosuppressed Macrophages in Colorectal Cancer. International journal of biological sciences 91 35541899
2007 Toll-like receptor 4 ligation on intrinsic renal cells contributes to the induction of antibody-mediated glomerulonephritis via CXCL1 and CXCL2. Journal of the American Society of Nephrology : JASN 90 17460147
2021 Group-2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2-Neutrophil-Induced Immunosuppression. Hepatology (Baltimore, Md.) 86 33829508
2014 SIRT2 Regulates LPS-Induced Renal Tubular CXCL2 and CCL2 Expression. Journal of the American Society of Nephrology : JASN 80 25349202
2014 The macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) in implant-associated osteomyelitis: linking inflammation to bone degradation. Mediators of inflammation 79 24795505
2006 Selective local PMN recruitment by CXCL1 or CXCL2/3 injection does not cause inflammatory pain. Journal of leukocyte biology 79 16522746
2018 Chemokine (C-X-C motif) ligand 1 and CXCL2 produced by tumor promote the generation of monocytic myeloid-derived suppressor cells. Cancer science 71 30259595
2023 Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury. Hepatology (Baltimore, Md.) 70 37695548
2016 Neutrophils Self-Regulate Immune Complex-Mediated Cutaneous Inflammation through CXCL2. The Journal of investigative dermatology 64 26802238
2007 CXCL1/KC and CXCL2/MIP-2 are critical effectors and potential targets for therapy of Escherichia coli O157:H7-associated renal inflammation. The American journal of pathology 63 17255321
2015 Loss of miR-532-5p in vitro promotes cell proliferation and metastasis by influencing CXCL2 expression in HCC. American journal of translational research 59 26807173
2008 Clostridium difficile toxin A promotes dendritic cell maturation and chemokine CXCL2 expression through p38, IKK, and the NF-kappaB signaling pathway. Journal of molecular medicine (Berlin, Germany) 59 18985311
2019 RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages. International immunopharmacology 58 31522017
2020 Functional heterogeneity of alveolar macrophage population based on expression of CXCL2. Science immunology 57 32769172
2018 CXCL2/CXCR2 axis induces cancer stem cell characteristics in CPT-11-resistant LoVo colon cancer cells via Gαi-2 and Gαq/11. Journal of cellular physiology 57 30552676
2015 Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes. Journal of cellular physiology 56 25708728
2023 Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps. Nature communications 53 36934105
2021 Macrophagic Extracellular Vesicle CXCL2 Recruits and Activates the Neutrophil CXCR2/PKC/NOX4 Axis in Sepsis. Journal of immunology (Baltimore, Md. : 1950) 51 34507947
2012 CCL2 and CXCL2 enhance survival of primary chronic lymphocytic leukemia cells in vitro. Leukemia & lymphoma 51 22397722
2010 Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis by Mip2/Cxcl2. Pediatric research 49 20234283
2024 The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression. Cell death & disease 48 38637499
2020 Omental adipocytes promote peritoneal metastasis of gastric cancer through the CXCL2-VEGFA axis. British journal of cancer 48 32439934
2020 PXR Functionally Interacts with NF-κB and AP-1 to Downregulate the Inflammation-Induced Expression of Chemokine CXCL2 in Mice. Cells 47 33076328
2014 Suppression of CXCL2 upregulation underlies the therapeutic effect of the retinoid Am80 on intracerebral hemorrhage in mice. Journal of neuroscience research 47 24659080
2012 Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells. Journal of cellular biochemistry 47 22615136
2019 CXCL2, a new critical factor and therapeutic target for cardiovascular diseases. Clinical and experimental hypertension (New York, N.Y. : 1993) 45 31752549
2021 The CXCL2/IL8/CXCR2 Pathway Is Relevant for Brain Tumor Malignancy and Endothelial Cell Function. International journal of molecular sciences 44 33807899
2021 Decreased miR-4512 Levels in Monocytes and Macrophages of Individuals With Systemic Lupus Erythematosus Contribute to Innate Immune Activation and Neutrsophil NETosis by Targeting TLR4 and CXCL2. Frontiers in immunology 43 34721432
2020 Herbal Combinational Medication of Glycyrrhiza glabra, Agastache rugosa Containing Glycyrrhizic Acid, Tilianin Inhibits Neutrophilic Lung Inflammation by Affecting CXCL2, Interleukin-17/STAT3 Signal Pathways in a Murine Model of COPD. Nutrients 43 32230838
2023 Schwann cell-derived CXCL2 contributes to cancer pain by modulating macrophage infiltration in a mouse breast cancer model. Brain, behavior, and immunity 42 36754246
2018 TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression. Cancer immunology, immunotherapy : CII 42 30251149
2019 The Clinicopathological Significance of the CXCR2 Ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in Gastric Cancer. Anticancer research 41 31810929
2021 CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells. Clinical & experimental metastasis 39 34115261
2021 Cis-acting lnc-Cxcl2 restrains neutrophil-mediated lung inflammation by inhibiting epithelial cell CXCL2 expression in virus infection. Proceedings of the National Academy of Sciences of the United States of America 38 34607953
2012 Induction of TNF-alfa and CXCL-2 mRNAs in different organs of mice infected with pathogenic Leptospira. Microbial pathogenesis 38 22342618
2008 Chemokine MIP-2/CXCL2, acting on CXCR2, induces motor neuron death in primary cultures. Neuroimmunomodulation 38 18391506
2025 CXCL2: a key player in the tumor microenvironment and inflammatory diseases. Cancer cell international 37 40197328
2020 The CXCR2/CXCL2 signalling pathway - An alternative therapeutic approach in high-grade glioma. European journal of cancer (Oxford, England : 1990) 37 31927212
2019 IL-10 and CXCL2 in trigeminal ganglia in neuropathic pain. Neuroscience letters 37 30904573
2018 TRPM2 Exacerbates Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis by Increasing Production of CXCL2 Chemokines. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 30201769
2016 The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2). Molecular immunology 37 27889620
2019 Transcriptome profiling analysis reveals that CXCL2 is involved in anlotinib resistance in human lung cancer cells. BMC medical genomics 36 30871526
2019 Neutrophils Enhance Their Own Influx to Sites of Bacterial Infection via Endosomal TLR-Dependent Cxcl2 Production. Journal of immunology (Baltimore, Md. : 1950) 36 31852751
2018 Overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis in hepatocellular carcinoma. BMB reports 35 30293547
2011 CXCL2 mediates lipopolysaccharide-induced osteoclastogenesis in RANKL-primed precursors. Cytokine 34 21507677
2023 Semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress mediated via reduction of neutrophil Cxcl2, S100a8, and S100a9 expression. Molecular and cellular biochemistry 33 37318712
2018 An IFNγ/CXCL2 regulatory pathway determines lesion localization during EAE. Journal of neuroinflammation 33 30012158
2024 METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis. Journal of experimental & clinical cancer research : CR 32 38605400
2021 Programmed Cell Death 10 Mediated CXCL2-CXCR2 Signaling in Regulating Tumor-Associated Microglia/Macrophages Recruitment in Glioblastoma. Frontiers in immunology 31 34108959
2017 11β-HSD1 suppresses cardiac fibroblast CXCL2, CXCL5 and neutrophil recruitment to the heart post MI. The Journal of endocrinology 31 28522730
2016 Site-Specific Neutrophil Migration and CXCL2 Expression in Periodontal Tissue. Journal of dental research 31 27013641
2014 Critical role of MKP-1 in lipopolysaccharide-induced osteoclast formation through CXCL1 and CXCL2. Cytokine 31 25261746
2023 Sirt4 deficiency promotes the development of atherosclerosis by activating the NF-κB/IκB/CXCL2/3 pathway. Atherosclerosis 28 37121164
2021 Cathepsin C aggravates neuroinflammation via promoting production of CCL2 and CXCL2 in glial cells and neurons in a cryogenic brain lesion. Neurochemistry international 28 34171415
2020 Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis. Clinical and experimental immunology 28 33010041
2012 CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction. Biochemical and biophysical research communications 28 22771802
2019 CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway. Journal of cell science 27 31292171
2018 Identification of genes and pathways, including the CXCL2 axis, altered by DNA methylation in hepatocellular carcinoma. Journal of cancer research and clinical oncology 27 30564899
2014 Daidzein suppresses pro-inflammatory chemokine Cxcl2 transcription in TNF-α-stimulated murine lung epithelial cells via depressing PARP-1 activity. Acta pharmacologica Sinica 26 24632845
2023 Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 23 36933379
2016 Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC. Scientific reports 23 27117207
2023 NFATc3 Promotes Pulmonary Inflammation and Fibrosis by Regulating Production of CCL2 and CXCL2 in Macrophages. Aging and disease 22 37523510
2007 A CXCL2 polymorphism is associated with better outcomes in patients with severe sepsis. Critical care medicine 22 17944017
2023 Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant. Journal of leukocyte biology 21 37625009
2006 Theiler's virus induces the MIP-2 chemokine (CXCL2) in astrocytes from genetically susceptible but not from resistant mouse strains. Cellular immunology 21 16684516
2023 Staphylococcus aureus Infection Induces the Production of the Neutrophil Chemoattractants CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL7 by Murine Osteoblasts. Infection and immunity 19 36880752
2015 Induction of CXCL2 and CCL2 by pressure force requires IL-1β-MyD88 axis in osteoblasts. Bone 19 25603464
2006 A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population. Genes and immunity 19 16421598
2004 Constitutive expression of CXCL2/MIP-2 is restricted to a Gr-1high, CD11b+, CD62Lhigh subset of bone marrow derived granulocytes. International immunology 19 15466452
2013 NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice. The Laryngoscope 18 23553435
2011 Expression of the inflammatory chemokines CCL2, CCL5 and CXCL2 and the receptors CCR1-3 and CXCR2 in T lymphocytes from mammary tumor-bearing mice. Cellular immunology 18 21621198
2022 Tumor-associated macrophages mediate gastrointestinal stromal tumor cell metastasis through CXCL2/CXCR2. Cellular immunology 17 36577281
2021 An inter-correlation among chemokine (C-X-C motif) ligand (CXCL) 1, CXCL2 and CXCL8, and their diversified potential as biomarkers for tumor features and survival profiles in non-small cell lung cancer patients. Translational cancer research 17 35116406
2012 ERK2-dependent activation of c-Jun is required for nontypeable Haemophilus influenzae-induced CXCL2 upregulation in inner ear fibrocytes. Journal of immunology (Baltimore, Md. : 1950) 17 22379036
2016 TIARP attenuates autoantibody-mediated arthritis via the suppression of neutrophil migration by reducing CXCL2/CXCR2 and IL-6 expression. Scientific reports 16 27995997
2021 CXCL2-mediated ATR/CHK1 signaling pathway and platinum resistance in epithelial ovarian cancer. Journal of ovarian research 15 34474677
2020 CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy. Molecular therapy oncolytics 15 33575480
2018 Differential binding of chemokines CXCL1, CXCL2 and CCL2 to mouse glomerular endothelial cells reveals specificity for distinct heparan sulfate domains. PloS one 15 30248108
2017 Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression. Journal of immunology (Baltimore, Md. : 1950) 15 28053238
2024 Quercetin protects against sepsis-associated encephalopathy by inhibiting microglia-neuron crosstalk via the CXCL2/CXCR2 signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 39216299
2023 Herbal formula Jiawei Xiaochengqi decoction prevents postoperative abdominal adhesion in a rat model through inhibition of CXCL2-CXCR2 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 36681054
2020 Tripterine Restrains the Aggressiveness of Hepatocellular Carcinoma Cell via Regulating miRNA-532-5p/CXCL2 Axis. OncoTargets and therapy 14 32308429
2019 Staphylococcus aureus infected embolic stroke upregulates Orm1 and Cxcl2 in a rat model of septic stroke pathology. Neurological research 14 30707086
2016 Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development. Basic & clinical pharmacology & toxicology 14 27194111
2022 Application of genomic selection and experimental techniques to predict cell death and immunotherapeutic efficacy of ferroptosis-related CXCL2 in hepatocellular carcinoma. Frontiers in oncology 13 36276119
2016 Retinoic acid receptor agonist Am80 inhibits CXCL2 production from microglial BV-2 cells via attenuation of NF-κB signaling. International immunopharmacology 13 27351827
2003 Expression of AMPA-type glutamate receptors in HEK cells and cerebellar granule neurons impairs CXCL2-mediated chemotaxis. Journal of neuroimmunology 13 12507773

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