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Gene Review

Cxcl1  -  chemokine (C-X-C motif) ligand 1

Mus musculus

Synonyms: C-X-C motif chemokine 1, Fsp, Gro, Gro1, Growth-regulated alpha protein, ...
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Disease relevance of Cxcl1


High impact information on Cxcl1

  • Impaired transepithelial migration was accompanied by a lack of both shed syndecan-1, a heparan sulfate proteoglycan, and KC, a CXC chemokine, in the alveolar fluid [6].
  • Two of these (KC and JE) were studied in detail [7].
  • This phosphorylation modulates its association with HDAC1, -3, and -6 and attenuates its oncogenicity by selectively controlling the expression of a subset of newly identified target genes such as SLPI and Cxcl1 [8].
  • Increased levels of the T cell-derived proinflammatory cytokine interleukin (IL)-17 and of neutrophil chemoattractant CXC chemokines macrophage inflammatory protein-2/CXCL8 and cytokine-induced neutrophil chemoattractant/CXCL1 were associated with adhesion formation [9].
  • We have found that two chemokines, recombinant gro-alpha and gro-beta, specifically inhibit growth factor-stimulated proliferation of capillary endothelial cells in a dose-dependent manner, whereas gro-gamma has no inhibitory effect [10].

Chemical compound and disease context of Cxcl1


Biological context of Cxcl1

  • Moreover, the expression of KC was parallel to the expression of the Duffy antigen binding protein for chemokines with regard to temporal pattern and tissue localization [14].
  • Inhibitors of protein synthesis block the progression of quiescent 3T3 cells through G1 into S phase; however these drugs do not block the induction of KC and JE by PDGF [7].
  • JE and KC downregulation by means of the AP-1 complex may play a role in the actions of glucocorticoids as anti-inflammatory and antitumor agents [15].
  • Although KC strongly increases Mac-1 expression on human PMN, it does not induce chemotaxis in vitro [11].
  • In these transgenic mice, doxycycline treatment induced a strong up-regulation in the expression of KC in several tissues, including heart, liver, kidney, skin, and skeletal muscle [16].

Anatomical context of Cxcl1

  • Surprisingly, neutrophil depletion before injury resulted in sustained high levels of both KC and MIP-2 expression [1].
  • The results of this study indicate 1) that the murine receptor for MIP-2 and KC, muCXCR2, plays a major role in neutrophil recruitment to s.c. tissue and the peritoneal cavity in response to proinflammatory agents and 2) that CXCR2 receptor antagonists prevent acute inflammation in vivo [17].
  • The murine CXC-chemokines macrophage inflammatory protein-2 (MIP-2) and KC induce migration of mouse mesangial cells [18].
  • Elevation of chemokine MIP-1beta, MIP-2, and KC mRNA levels induced by C. albicans was not affected in macrophages whose MR expression was suppressed by antisense ODN treatment [19].
  • By ELISA, KC protein was significantly elevated in Ad37-injected corneas at 8 and 16 hours, and MCP-1 protein at 16 hours after injection (P < 0.05) [20].

Associations of Cxcl1 with chemical compounds

  • KC was elevated at 1 h, and peaked at 6 h following LPS [21].
  • Oral administration of ethanol significantly suppressed HIV-1gp120-induced KC and RANTES release [5].
  • These myocytes also released the CXC chemokines LIX and KC; an event prevented by MG 132 [22].
  • Doxycycline treatment of nontransgenic mice grafted with transgenic skin caused dense neutrophilic infiltration of the grafts, but not the surrounding host skin, indicating that the KC produced in transgenic tissues was biologically active [16].
  • The expression of mRNA for c-fos could be readily induced by treatment of macrophages with phorbol myristate acetate (PMA) alone and that for JE by PMA plus the inophore A23187; mRNA for KC was largely unaffected by these agents [23].

Physical interactions of Cxcl1

  • Overexpression of a human Ikappa(B)alpha dominant suppresser in Pam 212 cells inhibited TNF-alpha-induced NF-kappaB binding activity and KC expression [24].

Regulatory relationships of Cxcl1


Other interactions of Cxcl1


Analytical, diagnostic and therapeutic context of Cxcl1

  • KC was bound to shed syndecan-1, and it was not detected in the lavage of syndecan-1 null mice [6].
  • Expression of these genes in control isografts was at low levels, with the exception of JE, which was expressed at equivalent levels in all iso- and allografts for the first 4-5 days posttransplant, and KC, which was expressed at equivalent levels in C57BL/6 isografts and bm1 and bm12 allografts [29].
  • The number of interstitial infiltrated neutrophils correlated well with serum levels of KC at 24 hrs after reperfusion, whereas the number of interstitial infiltrated macrophages correlated well with the serum levels of MIP-1alpha and monocyte chemoattractant protein (MCP)-1 at 24 and 48 hrs after reperfusion, respectively [30].
  • The murine counterpart of the above human genes has been reported to be the chemokine CXCL1 or KC, and therefore we studied its regulation, confirming its mRNA increase by Northern blots [4].
  • Cigarette smoke exposure for 3 days induced a time-dependent airway neutrophilia associated with an increased level of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, MIP-1alpha and MMP-9 in the bronchoalveolar lavage (BAL) [31].


  1. Distinct temporal patterns of macrophage-inflammatory protein-2 and KC chemokine gene expression in surgical injury. Endlich, B., Armstrong, D., Brodsky, J., Novotny, M., Hamilton, T.A. J. Immunol. (2002) [Pubmed]
  2. Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2. Brown, C.R., Blaho, V.A., Loiacono, C.M. J. Immunol. (2003) [Pubmed]
  3. Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. Glabinski, A.R., Tani, M., Strieter, R.M., Tuohy, V.K., Ransohoff, R.M. Am. J. Pathol. (1997) [Pubmed]
  4. Induction of the CXCL1 (KC) chemokine in mouse astrocytes by infection with the murine encephalomyelitis virus of Theiler. Rubio, N., Sanz-Rodriguez, F. Virology (2007) [Pubmed]
  5. Acute ethanol administration downregulates human immunodeficiency virus-1 glycoprotein 120-induced KC and RANTES production by murine Kupffer cells and splenocytes. Bautista, A.P., Wang, E. Life Sci. (2002) [Pubmed]
  6. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Li, Q., Park, P.W., Wilson, C.L., Parks, W.C. Cell (2002) [Pubmed]
  7. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cochran, B.H., Reffel, A.C., Stiles, C.D. Cell (1983) [Pubmed]
  8. GSK3-mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity. Viatour, P., Dejardin, E., Warnier, M., Lair, F., Claudio, E., Bureau, F., Marine, J.C., Merville, M.P., Maurer, U., Green, D., Piette, J., Siebenlist, U., Bours, V., Chariot, A. Mol. Cell (2004) [Pubmed]
  9. CD4+ T cells regulate surgical and postinfectious adhesion formation. Chung, D.R., Chitnis, T., Panzo, R.J., Kasper, D.L., Sayegh, M.H., Tzianabos, A.O. J. Exp. Med. (2002) [Pubmed]
  10. gro-beta, a -C-X-C- chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice. Cao, Y., Chen, C., Weatherbee, J.A., Tsang, M., Folkman, J. J. Exp. Med. (1995) [Pubmed]
  11. Expression and biologic characterization of the murine chemokine KC. Bozic, C.R., Kolakowski, L.F., Gerard, N.P., Garcia-Rodriguez, C., von Uexkull-Guldenband, C., Conklyn, M.J., Breslow, R., Showell, H.J., Gerard, C. J. Immunol. (1995) [Pubmed]
  12. Protective effects of isoflurane pretreatment in endotoxin-induced lung injury. Reutershan, J., Chang, D., Hayes, J.K., Ley, K. Anesthesiology (2006) [Pubmed]
  13. Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease. Mohsenin, A., Burdick, M.D., Molina, J.G., Keane, M.P., Blackburn, M.R. FASEB J. (2007) [Pubmed]
  14. Developmental expression of two CXC chemokines, MIP-2 and KC, and their receptors. Luan, J., Furuta, Y., Du, J., Richmond, A. Cytokine (2001) [Pubmed]
  15. Downregulation of JE and KC genes by glucocorticoids does not prevent the G0----G1 transition in BALB/3T3 cells. Rameh, L.E., Armelin, M.C. Mol. Cell. Biol. (1992) [Pubmed]
  16. Disruption of neutrophil migration in a conditional transgenic model: evidence for CXCR2 desensitization in vivo. Wiekowski, M.T., Chen, S.C., Zalamea, P., Wilburn, B.P., Kinsley, D.J., Sharif, W.W., Jensen, K.K., Hedrick, J.A., Manfra, D., Lira, S.A. J. Immunol. (2001) [Pubmed]
  17. Inhibition of murine neutrophil recruitment in vivo by CXC chemokine receptor antagonists. McColl, S.R., Clark-Lewis, I. J. Immunol. (1999) [Pubmed]
  18. Chemokine amplification in mesangial cells. Luo, Y., Lloyd, C., Gutierrez-Ramos, J.C., Dorf, M.E. J. Immunol. (1999) [Pubmed]
  19. Involvement of mannose receptor in cytokine interleukin-1beta (IL-1beta), IL-6, and granulocyte-macrophage colony-stimulating factor responses, but not in chemokine macrophage inflammatory protein 1beta (MIP-1beta), MIP-2, and KC responses, caused by attachment of Candida albicans to macrophages. Yamamoto, Y., Klein, T.W., Friedman, H. Infect. Immun. (1997) [Pubmed]
  20. Adenovirus Type 37 Keratitis in the C57BL/6J Mouse. Chintakuntlawar, A.V., Astley, R., Chodosh, J. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  21. Selective chemokine mRNA expression following brain injury. Hausmann, E.H., Berman, N.E., Wang, Y.Y., Meara, J.B., Wood, G.W., Klein, R.M. Brain Res. (1998) [Pubmed]
  22. Cardiac myocytes activated by septic plasma promote neutrophil transendothelial migration: role of platelet-activating factor and the chemokines LIX and KC. Madorin, W.S., Rui, T., Sugimoto, N., Handa, O., Cepinskas, G., Kvietys, P.R. Circ. Res. (2004) [Pubmed]
  23. The effect of LPS on expression of the early "competence" genes JE and KC in murine peritoneal macrophages. Introna, M., Bast, R.C., Tannenbaum, C.S., Hamilton, T.A., Adams, D.O. J. Immunol. (1987) [Pubmed]
  24. The host environment promotes the constitutive activation of nuclear factor-kappaB and proinflammatory cytokine expression during metastatic tumor progression of murine squamous cell carcinoma. Dong, G., Chen, Z., Kato, T., Van Waes, C. Cancer Res. (1999) [Pubmed]
  25. IFN-gamma selectively inhibits lipopolysaccharide-inducible JE/monocyte chemoattractant protein-1 and KC/GRO/melanoma growth-stimulating activity gene expression in mouse peritoneal macrophages. Ohmori, Y., Hamilton, T.A. J. Immunol. (1994) [Pubmed]
  26. Expression of proangiogenic chemokine Gro 1 in low and high metastatic variants of Pam murine squamous cell carcinoma is differentially regulated by IL-1alpha, EGF and TGF-beta1 through NF-kappaB dependent and independent mechanisms. Loukinova, E., Chen, Z., Van Waes, C., Dong, G. Int. J. Cancer (2001) [Pubmed]
  27. Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone. Schramm, R., Schaefer, T., Menger, M.D., Thorlacius, H. J. Leukoc. Biol. (2002) [Pubmed]
  28. Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo. Kopydlowski, K.M., Salkowski, C.A., Cody, M.J., van Rooijen, N., Major, J., Hamilton, T.A., Vogel, S.N. J. Immunol. (1999) [Pubmed]
  29. Induction of chemokine gene expression during allogeneic skin graft rejection. Kondo, T., Novick, A.C., Toma, H., Fairchild, R.L. Transplantation (1996) [Pubmed]
  30. Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury. Furuichi, K., Wada, T., Iwata, Y., Kokubo, S., Hara, A., Yamahana, J., Sugaya, T., Iwakura, Y., Matsushima, K., Asano, M., Yokoyama, H., Kaneko, S. Crit. Care Med. (2006) [Pubmed]
  31. Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice. Leclerc, O., Lagente, V., Planquois, J.M., Berthelier, C., Artola, M., Eichholtz, T., Bertrand, C.P., Schmidlin, F. Eur. Respir. J. (2006) [Pubmed]
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