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Gene Review

CXCL6  -  chemokine (C-X-C motif) ligand 6

Homo sapiens

Synonyms: C-X-C motif chemokine 6, CKA-3, Chemokine alpha 3, GCP-2, GCP2, ...
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Disease relevance of CXCL6


High impact information on CXCL6

  • To conclude, our findings shed light on the interrelationships between GCP-2 and other ELR(+)-CXC chemokines, and determine the mechanisms involved in the regulation of GCP-2-induced internalization and recycling of CXCR2 [4].
  • Three of the 10 transcripts encoded CXC chemokines (CXCL1, CXCL2, and CXCL6) [5].
  • These data confirm that sIL-6R-mediated signaling primarily limits neutrophil influx; however, induction of CXCL5 and CXCL6 may regulate other neutrophil responses [6].
  • Neutralization experiments indicated that chemotaxis was mainly mediated by CXCL8, but not by granulocyte chemotactic protein-2/CXCL6, epithelial cell-derived neutrophil attractant-78/CXCL5, or growth-related oncogene-alpha,beta,gamma/CXCL1,2,3 [7].
  • Both concentrations are similar to the effective concentrations of IL-8 and less than the effective concentrations of other neutrophil chemoattractants such as neutrophil-activating peptide-78, granulocyte chemotactic protein-2, leukotriene B(4), and FMLP [8].

Chemical compound and disease context of CXCL6


Biological context of CXCL6


Anatomical context of CXCL6


Associations of CXCL6 with chemical compounds

  • A variant of GCP-2 in which the basic residue, Arg20, was replaced by a glycine was synthesized [15].
  • When compared with epithelial-cell-derived neutrophil-activating peptide-78 (ENA-78) mRNA, the GCP-2 mRNA levels were higher in all cell lines tested [9].

Physical interactions of CXCL6


Regulatory relationships of CXCL6


Other interactions of CXCL6

  • This derivative was ineffective on CXCR1, but was as active as wild-type GCP-2 in CXCR2-expressing cells [15].
  • Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is the functional homologue for human CXCL6 [18].
  • The differential receptor usage of the structurally related ELR+ CXC chemokines GCP-2 and ENA-78 is indicative of a different role in inflammatory reactions [19].
  • In contrast with its weak proliferative effect on endothelial cells, GCP-2 synergized with MCP-1 in neutrophil chemotaxis [14].
  • GCP-2 may serve as a substitute chemokine in certain inflammatory conditions as its quantity of mRNA and protein was higher in RT and PA than in HT [20].

Analytical, diagnostic and therapeutic context of CXCL6


  1. Production and upregulation of granulocyte chemotactic protein-2/CXCL6 by IL-1beta and hypoxia in small cell lung cancer. Zhu, Y.M., Bagstaff, S.M., Woll, P.J. Br. J. Cancer (2006) [Pubmed]
  2. The CXC chemokine GCP-2/CXCL6 is predominantly induced in mesenchymal cells by interleukin-1beta and is down-regulated by interferon-gamma: comparison with interleukin-8/CXCL8. Wuyts, A., Struyf, S., Gijsbers, K., Schutyser, E., Put, W., Conings, R., Lenaerts, J.P., Geboes, K., Opdenakker, G., Menten, P., Proost, P., Van Damme, J. Lab. Invest. (2003) [Pubmed]
  3. Neutrophil chemokines in epithelial inflammatory processes of human tonsils. Sachse, F., Ahlers, F., Stoll, W., Rudack, C. Clin. Exp. Immunol. (2005) [Pubmed]
  4. GCP-2-induced internalization of IL-8 receptors: hierarchical relationships between GCP-2 and other ELR(+)-CXC chemokines and mechanisms regulating CXCR2 internalization and recycling. Feniger-Barish, R., Belkin, D., Zaslaver, A., Gal, S., Dori, M., Ran, M., Ben-Baruch, A. Blood (2000) [Pubmed]
  5. Extremely low dose ionizing radiation up-regulates CXC chemokines in normal human fibroblasts. Fujimori, A., Okayasu, R., Ishihara, H., Yoshida, S., Eguchi-Kasai, K., Nojima, K., Ebisawa, S., Takahashi, S. Cancer Res. (2005) [Pubmed]
  6. Differential regulation of neutrophil-activating chemokines by IL-6 and its soluble receptor isoforms. McLoughlin, R.M., Hurst, S.M., Nowell, M.A., Harris, D.A., Horiuchi, S., Morgan, L.W., Wilkinson, T.S., Yamamoto, N., Topley, N., Jones, S.A. J. Immunol. (2004) [Pubmed]
  7. Characterization of human T cells that regulate neutrophilic skin inflammation. Schaerli, P., Britschgi, M., Keller, M., Steiner, U.C., Steinmann, L.S., Moser, B., Pichler, W.J. J. Immunol. (2004) [Pubmed]
  8. Granulocyte-macrophage colony-stimulating factor is a chemoattractant cytokine for human neutrophils: involvement of the ribosomal p70 S6 kinase signaling pathway. Gomez-Cambronero, J., Horn, J., Paul, C.C., Baumann, M.A. J. Immunol. (2003) [Pubmed]
  9. Cloning, bacterial expression and biological characterization of recombinant human granulocyte chemotactic protein-2 and differential expression of granulocyte chemotactic protein-2 and epithelial cell-derived neutrophil activating peptide-78 mRNAs. Froyen, G., Proost, P., Ronsse, I., Mitera, T., Haelens, A., Wuyts, A., Opdenakker, G., Van Damme, J., Billiau, A. Eur. J. Biochem. (1997) [Pubmed]
  10. Characterization of synthetic human granulocyte chemotactic protein 2: usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties. Wuyts, A., Van Osselaer, N., Haelens, A., Samson, I., Herdewijn, P., Ben-Baruch, A., Oppenheim, J.J., Proost, P., Van Damme, J. Biochemistry (1997) [Pubmed]
  11. Cloning and characterization of the human granulocyte chemotactic protein-2 gene. Rovai, L.E., Herschman, H.R., Smith, J.B. J. Immunol. (1997) [Pubmed]
  12. Differential regulation of ENA-78 and GCP-2 gene expression in human corneal keratocytes and epithelial cells. Fillmore, R.A., Nelson, S.E., Lausch, R.N., Oakes, J.E. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  13. CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue. Gijsbers, K., Van Assche, G., Joossens, S., Struyf, S., Proost, P., Rutgeerts, P., Geboes, K., Van Damme, J. Eur. J. Immunol. (2004) [Pubmed]
  14. GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors. Gijsbers, K., Gouwy, M., Struyf, S., Wuyts, A., Proost, P., Opdenakker, G., Penninckx, F., Ectors, N., Geboes, K., Van Damme, J. Exp. Cell Res. (2005) [Pubmed]
  15. Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. Wolf, M., Delgado, M.B., Jones, S.A., Dewald, B., Clark-Lewis, I., Baggiolini, M. Eur. J. Immunol. (1998) [Pubmed]
  16. Chemokine regulation of neutrophil function in surgical inflammation. Williams, M.A., Cave, C.M., Quaid, G., Solomkin, J.S. Archives of surgery (Chicago, Ill. : 1960) (1999) [Pubmed]
  17. Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage. Van Damme, J., Wuyts, A., Froyen, G., Van Coillie, E., Struyf, S., Billiau, A., Proost, P., Wang, J.M., Opdenakker, G. J. Leukoc. Biol. (1997) [Pubmed]
  18. Rabbit neutrophil chemotactic protein (NCP) activates both CXCR1 and CXCR2 and is the functional homologue for human CXCL6. Catusse, J., Struyf, S., Wuyts, A., Weyler, M., Loos, T., Gijsbers, K., Gouwy, M., Proost, P., Van Damme, J. Biochem. Pharmacol. (2004) [Pubmed]
  19. Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78. Wuyts, A., Proost, P., Lenaerts, J.P., Ben-Baruch, A., Van Damme, J., Wang, J.M. Eur. J. Biochem. (1998) [Pubmed]
  20. Biologically active neutrophil chemokine pattern in tonsillitis. Rudack, C., Jörg, S., Sachse, F. Clin. Exp. Immunol. (2004) [Pubmed]
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