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Gene Review

CXCL2  -  chemokine (C-X-C motif) ligand 2

Homo sapiens

Synonyms: C-X-C motif chemokine 2, CINC-2a, GRO2, GROB, GROb, ...
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Disease relevance of CXCL2

  • In addition, the melanoma growth and migration stimulatory chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts [1].
  • In contrast, CFA injection induced hyperalgesia, independent of PMN recruitment. c-Fos mRNA and immunoreactivity in the spinal cord were increased significantly after inoculation of CFA-independent of PMN-migration but not of CXCL2/3 [2].
  • Although replicate studies and functional assays are needed, these results suggest that CXCL2 gene variants may contribute to the development of severe sepsis [3].
  • LPS-induced MIP-2 production by bronchoalveolar cells and liver mononuclear cells in mice with peritonitis was also significantly increased compared with sham-operated mice [4].
  • In the spinal cord, parenchymal invasion, demyelination and clinical symptoms are associated with TNFR1-dependant parenchymal induction (especially astrocytes) of VCAM-1 and CXCL2 [5].

Psychiatry related information on CXCL2


High impact information on CXCL2


Chemical compound and disease context of CXCL2

  • CONCLUSIONS: Ang II provokes rapid neutrophil recruitment, mediated through the release of CXC chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may contribute to the infiltration of neutrophils observed in acute myocardial infarction [11].
  • The aim of the present study was to examine the role of a CXC chemokine, macrophage inflammatory protein-2 (MIP-2), in the hepatotoxic response by mice infected with adenovirus and challenged with acetaminophen [12].
  • Thioglycollate (thio) and glycogen (gly) induced peritonitis produced more KC (thio = 7.1 and gly = 2.5 ng/mL) in the peritoneum compared with MIP2 (thio = 4.5 and gly = 0.3 ng/mL) [13].
  • Alveolar macrophages obtained after induction of pancreatitis generated increased levels of nitric oxide, tumor necrosis factor-alpha, and MIP-2, but not leukotriene B4 [14].
  • Omphalocele is a disease of neonatal age and its present management is successful in almost all specialized centers of Pediatric Surgery. A case of an 8-year-old girl who was managed with conservative treatment during her neonatal period with mercurochrome (Grob method) is presented [15].

Biological context of CXCL2


Anatomical context of CXCL2

  • Previous work has demonstrated that microglia produce CCL2, and here we demonstrate that astrocytes and endothelial cells produced CXCL2 in the early stages of inflammation [19].
  • Taken together, these results suggest that the association between CXCR2 and AMPARs results in the inhibition of CXCL2-dependent chemotaxis, and may represent a molecular mechanism underlying the modulation of nerve cell migration [16].
  • These studies demonstrate the importance of the CXCR2 ligands MIP-2 and KC and neutrophils in the acute host response to S. aureus in the brain [20].
  • Our results demonstrate that constitutive expression of MIP-2 in INK4a/ARF-deficient melanocytes facilitates formation of malignant melanoma [6].
  • Transient expression of the murine receptor cDNA in COS cells conferred binding ability to KC and a related gene product, macrophage inflammatory protein-2 (MIP-2) with high affinity (approximately 5 nM) [21].

Associations of CXCL2 with chemical compounds

  • This study instead demonstrates that preincubation of AECs with an antibody directed against the membrane glycosphingolipid lactosylceramide (CDw17) results in a significant decrease in MIP-2 secretion [22].
  • Herein, we demonstrate that a PC beta-glucan rich cell wall isolate (PCBG) stimulates the release of macrophage inflammatory protein-2 (MIP-2) from isolated AECs through a lactosylceramide-dependent mechanism [22].
  • These data demonstrate that PC beta-glucan induces significant production of MIP-2 from AECs and that CDw17 participates in the glucan-induced inflammatory signaling in lung epithelial cells during PC infection [22].
  • We therefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine-induced neutrophil chemoattractant-1 (CINC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung [23].
  • Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/keratinocyte-derived chemokine, macrophage inflammatory protein-2 (MIP-2), and platelet-activating factor (PAF) elicited by Ang-II, SB only reduced the release of MIP-2 after 4 h of its administration [24].

Regulatory relationships of CXCL2


Other interactions of CXCL2

  • IL-8 and Gro-beta (CXC) and lymphotactin (C chemokines) were also inactive [26].
  • We find that cerebellar granule neurons (CGN) obtained from newborn rats (p3) migrate in response to both CXC chemokine ligand-2 (CXCL2) and -12 (CXCL12), while CGN from p7 rats are unresponsive to CXCL2 [16].
  • No difference in CXCL2 and CXCL3 mRNA expression levels was observed [27].
  • In rats with hindpaw inflammation, intraplantar injection of CXCL2/3, but not of the CXCR4 ligand CXCL12, elicited naloxone-reversible (i.e., opioid receptor mediated) mechanical and thermal analgesia, which was abolished by systemic PMN depletion [28].
  • Other cytokines that are primarily involved in this inflammatory response include IFN-gamma, MCP-1, and MIP-2 [29].

Analytical, diagnostic and therapeutic context of CXCL2

  • Functional studies in animal models of sepsis have catalogued CXCL2 as a candidate gene for the development of the disease [3].
  • Adoptive transfer of allogenic PMN into PMN-depleted rats reconstituted CXCL2/3-induced analgesia, which was inhibited by prior ex vivo chelation of intracellular Ca2+ [28].
  • Circular dichroism spectroscopy reveals that MIP-2 exhibits a highly ordered secondary structure consistent with the alpha/beta structures of other chemokines [30].
  • MIP-2 protein was detected in bronchoalveolar lavage fluids of these animals and a significant amount of chemotactic activity present in these fluids was attributed to MIP-2 [31].
  • This observation was verified with qualitative reverse transcriptase-PCR and ELISA in human endothelial cell culture, and in a mouse model by observing serum levels of MIP-2 and KC following hyaluronan fragment administration in vivo [32].


  1. Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis. Gallagher, P.G., Bao, Y., Prorock, A., Zigrino, P., Nischt, R., Politi, V., Mauch, C., Dragulev, B., Fox, J.W. Cancer Res. (2005) [Pubmed]
  2. Selective local PMN recruitment by CXCL1 or CXCL2/3 injection does not cause inflammatory pain. Rittner, H.L., Mousa, S.A., Labuz, D., Beschmann, K., Schäfer, M., Stein, C., Brack, A. J. Leukoc. Biol. (2006) [Pubmed]
  3. A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population. Flores, C., Maca-Meyer, N., Pérez-Méndez, L., Sangüesa, R., Espinosa, E., Muriel, A., Blanco, J., Villar, J. Genes Immun. (2006) [Pubmed]
  4. Neutrophil elastase, MIP-2, and TLR-4 expression during human and experimental sepsis. Tsujimoto, H., Ono, S., Majima, T., Kawarabayashi, N., Takayama, E., Kinoshita, M., Seki, S., Hiraide, H., Moldawer, L.L., Mochizuki, H. Shock (2005) [Pubmed]
  5. Region-specific regulation of inflammation and pathogenesis in experimental autoimmune encephalomyelitis. Archambault, A.S., Sim, J., McCandless, E.E., Klein, R.S., Russell, J.H. J. Neuroimmunol. (2006) [Pubmed]
  6. Induction of melanoma in murine macrophage inflammatory protein 2 transgenic mice heterozygous for inhibitor of kinase/alternate reading frame. Yang, J., Luan, J., Yu, Y., Li, C., DePinho, R.A., Chin, L., Richmond, A. Cancer Res. (2001) [Pubmed]
  7. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Zhao, L., Moos, M.P., Gräbner, R., Pédrono, F., Fan, J., Kaiser, B., John, N., Schmidt, S., Spanbroek, R., Lötzer, K., Huang, L., Cui, J., Rader, D.J., Evans, J.F., Habenicht, A.J., Funk, C.D. Nat. Med. (2004) [Pubmed]
  8. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. Lotz, M., Gütle, D., Walther, S., Ménard, S., Bogdan, C., Hornef, M.W. J. Exp. Med. (2006) [Pubmed]
  9. Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. Biedermann, T., Kneilling, M., Mailhammer, R., Maier, K., Sander, C.A., Kollias, G., Kunkel, S.L., Hültner, L., Röcken, M. J. Exp. Med. (2000) [Pubmed]
  10. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. Tekamp-Olson, P., Gallegos, C., Bauer, D., McClain, J., Sherry, B., Fabre, M., van Deventer, S., Cerami, A. J. Exp. Med. (1990) [Pubmed]
  11. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Nabah, Y.N., Mateo, T., Estellés, R., Mata, M., Zagorski, J., Sarau, H., Cortijo, J., Morcillo, E.J., Jose, P.J., Sanz, M.J. Circulation (2004) [Pubmed]
  12. Macrophage inflammatory protein-2 gene therapy attenuates adenovirus- and acetaminophen-mediated hepatic injury. Hogaboam, C.M., Simpson, K.J., Chensue, S.W., Steinhauser, M.L., Lukacs, N.W., Gauldie, J., Strieter, R.M., Kunkel, S.L. Gene Ther. (1999) [Pubmed]
  13. Differential local and systemic regulation of the murine chemokines KC and MIP2. Call, D.R., Nemzek, J.A., Ebong, S.J., Bolgos, G.R., Newcomb, D.E., Wollenberg, G.K., Remick, D.G. Shock (2001) [Pubmed]
  14. Activation of alveolar macrophages in lung injury associated with experimental acute pancreatitis is mediated by the liver. Closa, D., Sabater, L., Fernández-Cruz, L., Prats, N., Gelpí, E., Roselló-Catafau, J. Ann. Surg. (1999) [Pubmed]
  15. Management of neglected giant omphalocele with Gore-tex in a child aged 8 years. Sakellaris, G., Petrakis, I., Vlazakis, S., Kakavelakis, K., Vasiliou, M., Antipas, S., Ntolatzas, T. Minerva Pediatr. (2002) [Pubmed]
  16. Expression of AMPA-type glutamate receptors in HEK cells and cerebellar granule neurons impairs CXCL2-mediated chemotaxis. Limatola, C., Di Bartolomeo, S., Trettel, F., Lauro, C., Ciotti, M.T., Mercanti, D., Castellani, L., Eusebi, F. J. Neuroimmunol. (2003) [Pubmed]
  17. Expression analysis of immune response genes of M??ller cells infected with Toxoplasma gondii. Knight, B.C., Kissane, S., Falciani, F., Salmon, M., Stanford, M.R., Wallace, G.R. J. Neuroimmunol. (2006) [Pubmed]
  18. Chemokine receptor CXCR2 regulates the functional properties of AMPA-type glutamate receptor GluR1 in HEK cells. Lax, P., Limatola, C., Fucile, S., Trettel, F., Di Bartolomeo, S., Renzi, M., Ragozzino, D., Eusebi, F. J. Neuroimmunol. (2002) [Pubmed]
  19. A tumor necrosis factor receptor 1-dependent conversation between central nervous system-specific T cells and the central nervous system is required for inflammatory infiltration of the spinal cord. Gimenez, M.A., Sim, J., Archambault, A.S., Klein, R.S., Russell, J.H. Am. J. Pathol. (2006) [Pubmed]
  20. CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses. Kielian, T., Barry, B., Hickey, W.F. J. Immunol. (2001) [Pubmed]
  21. The murine interleukin 8 type B receptor homologue and its ligands. Expression and biological characterization. Bozic, C.R., Gerard, N.P., von Uexkull-Guldenband, C., Kolakowski, L.F., Conklyn, M.J., Breslow, R., Showell, H.J., Gerard, C. J. Biol. Chem. (1994) [Pubmed]
  22. Pneumocystis carinii cell wall beta-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramide-mediated mechanism. Hahn, P.Y., Evans, S.E., Kottom, T.J., Standing, J.E., Pagano, R.E., Limper, A.H. J. Biol. Chem. (2003) [Pubmed]
  23. Lung inflammation in hyperoxia can be prevented by antichemokine treatment in newborn rats. Deng, H., Mason, S.N., Auten, R.L. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  24. Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo. Estellés, R., Milian, L., Nabah, Y.N., Mateo, T., Cerdá-Nicolás, M., Losada, M., Ivorra, M.D., Issekutz, A.C., Cortijo, J., Morcillo, E.J., Blázquez, M.A., Sanz, M.J. J. Leukoc. Biol. (2005) [Pubmed]
  25. Mullerian-inhibiting substance induces Gro-beta expression in breast cancer cells through a nuclear factor-kappaB-dependent and Smad1-dependent mechanism. Gupta, V., Yeo, G., Kawakubo, H., Rangnekar, V., Ramaswamy, P., Hayashida, T., MacLaughlin, D.T., Donahoe, P.K., Maheswaran, S. Cancer Res. (2007) [Pubmed]
  26. Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. Sozzani, S., Luini, W., Borsatti, A., Polentarutti, N., Zhou, D., Piemonti, L., D'Amico, G., Power, C.A., Wells, T.N., Gobbi, M., Allavena, P., Mantovani, A. J. Immunol. (1997) [Pubmed]
  27. Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic phenotype. Li, A., Varney, M.L., Singh, R.K. Clin. Exp. Metastasis (2004) [Pubmed]
  28. Pain control by CXCR2 ligands through Ca2+-regulated release of opioid peptides from polymorphonuclear cells. Rittner, H.L., Labuz, D., Schaefer, M., Mousa, S.A., Schulz, S., Sch??fer, M., Stein, C., Brack, A. FASEB J. (2006) [Pubmed]
  29. Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Bhandari, V., Elias, J.A. Free Radic. Biol. Med. (2006) [Pubmed]
  30. Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: sequence analysis and mutagenesis identify receptor binding epitopes. Jerva, L.F., Sullivan, G., Lolis, E. Protein Sci. (1997) [Pubmed]
  31. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats. Schmal, H., Shanley, T.P., Jones, M.L., Friedl, H.P., Ward, P.A. J. Immunol. (1996) [Pubmed]
  32. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. Taylor, K.R., Trowbridge, J.M., Rudisill, J.A., Termeer, C.C., Simon, J.C., Gallo, R.L. J. Biol. Chem. (2004) [Pubmed]
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