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Gene Review

CXCL5  -  chemokine (C-X-C motif) ligand 5

Homo sapiens

Synonyms: C-X-C motif chemokine 5, ENA-78, ENA-78(1-78), ENA78, Epithelial-derived neutrophil-activating protein 78, ...
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Disease relevance of CXCL5


High impact information on CXCL5

  • Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8 [5].
  • Like NAP-2 and GRO alpha, ENA-78 stimulates neutrophils, inducing chemotaxis, a rise in intracellular free calcium and exocytosis [5].
  • A new neutrophil-activating peptide, termed ENA-78, was identified in the conditioned media of stimulated human type II epithelial cell line A549 [5].
  • In a SCID mouse model of human NSCLC tumorigenesis, expression of ENA-78 in developing tumors correlated with tumor growth in two different NSCLC cell lines [6].
  • Furthermore, passive immunization of NSCLC tumor-bearing mice with neutralizing anti-ENA-78 antibodies reduced tumor growth, tumor vascularity, and spontaneous metastases, while having no effect on the proliferation of NSCLC cells either in vitro or in vivo [6].

Chemical compound and disease context of CXCL5


Biological context of CXCL5

  • By measuring calcium flux in human embryonic kidney 293 cells transfected with plasmids encoding IL8RA or IL8RB, we have now defined receptor selectivity for GRObeta, GROgamma, and ENA-78 [9].
  • Interleukin-8 (IL-8) and closely related Glu-Leu-Arg (ELR) containing CXC chemokines, including growth-related oncogene (GRO)alpha, GRObeta, GROgamma, and epithelial cell-derived neutrophil-activating peptide-78 (ENA-78), are potent neutrophil chemotactic and activating peptides, which are proposed to be major mediators of inflammation [10].
  • The human ENA-78 gene was mapped to chromosome 4q13-q21, the same locus as several other inflammatory cytokine genes [11].
  • Despite 85% identity of the first 270 nucleotides 5' of the transcription start sites, GCP-2 and ENA-78 show cell-specific differences in regulation [12].
  • Infected endometrial cells demonstrated up-regulation of ENA-78 and GCP-2 chemokine mRNA [13].

Anatomical context of CXCL5


Associations of CXCL5 with chemical compounds

  • Preincubation with IL-8, MGSA, or ENA-78 enhanced the ability of neutrophils to generate O-2 following stimulation with the bacterial peptide formyl-Met-Leu-Phe [17].
  • Isolation of the CXC chemokines ENA-78, GRO alpha and GRO gamma from tumor cells and leukocytes reveals NH2-terminal heterogeneity. Functional comparison of different natural isoforms [18].
  • RA synovial fluid mononuclear cells spontaneously produced ENA-78, which was augmented in the presence of lipopolysaccharide [19].
  • (3) The oxidized low density lipoprotein-induced release of ENA-78 from peripheral blood mononuclear cells from control subjects was significantly reduced when cells were incubated in the presence of folic acid [20].
  • Data showed the following: (1) Compared with control subjects, hyperhomocysteinemic subjects had elevated plasma levels of the CXC chemokines, epithelial neutrophil-activating peptide (ENA)-78 (P<0.05), and growth-regulated oncogene (GRO)alpha (P=0.088), and homocysteine was significantly correlated with ENA-78 and GROalpha [20].

Regulatory relationships of CXCL5


Other interactions of CXCL5


Analytical, diagnostic and therapeutic context of CXCL5


  1. Chemotactic activity of CXCL5 in cerebrospinal fluid of children with bacterial meningitis. Zwijnenburg, P.J., de Bie, H.M., Roord, J.J., van der Poll, T., van Furth, A.M. J. Neuroimmunol. (2003) [Pubmed]
  2. Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease. Walz, A., Schmutz, P., Mueller, C., Schnyder-Candrian, S. J. Leukoc. Biol. (1997) [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. Disrupted expression of CXCL5 in colorectal cancer is associated with rapid tumor formation in rats and poor prognosis in patients. Speetjens, F.M., Kuppen, P.J., Sandel, M.H., Menon, A.G., Burg, D., van de Velde, C.J., Tollenaar, R.A., de Bont, H.J., Nagelkerke, J.F. Clin. Cancer Res. (2008) [Pubmed]
  5. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. Walz, A., Burgener, R., Car, B., Baggiolini, M., Kunkel, S.L., Strieter, R.M. J. Exp. Med. (1991) [Pubmed]
  6. Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer. Arenberg, D.A., Keane, M.P., DiGiovine, B., Kunkel, S.L., Morris, S.B., Xue, Y.Y., Burdick, M.D., Glass, M.C., Iannettoni, M.D., Strieter, R.M. J. Clin. Invest. (1998) [Pubmed]
  7. Peritoneal fluid concentrations of epithelial neutrophil-activating peptide-78 correlate with the severity of endometriosis. Suzumori, N., Katano, K., Suzumori, K. Fertil. Steril. (2004) [Pubmed]
  8. Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy. Chegini, N., Luo, X., Pan, Q., Rhoton-Vlasak, A., Archer, D.F. Hum. Reprod. (2007) [Pubmed]
  9. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. Ahuja, S.K., Murphy, P.M. J. Biol. Chem. (1996) [Pubmed]
  10. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. White, J.R., Lee, J.M., Young, P.R., Hertzberg, R.P., Jurewicz, A.J., Chaikin, M.A., Widdowson, K., Foley, J.J., Martin, L.D., Griswold, D.E., Sarau, H.M. J. Biol. Chem. (1998) [Pubmed]
  11. Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene. Chang, M.S., McNinch, J., Basu, R., Simonet, S. J. Biol. Chem. (1994) [Pubmed]
  12. Cloning and characterization of the human granulocyte chemotactic protein-2 gene. Rovai, L.E., Herschman, H.R., Smith, J.B. J. Immunol. (1997) [Pubmed]
  13. Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis. Wyrick, P.B., Knight, S.T., Paul, T.R., Rank, R.G., Barbier, C.S. J. Infect. Dis. (1999) [Pubmed]
  14. 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]
  15. Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils. Persson, T., Monsef, N., Andersson, P., Bjartell, A., Malm, J., Calafat, J., Egesten, A. Clin. Exp. Allergy (2003) [Pubmed]
  16. Chemokines and their receptors in the pathogenesis of allergic asthma: progress and perspective. Bisset, L.R., Schmid-Grendelmeier, P. Current opinion in pulmonary medicine. (2005) [Pubmed]
  17. Interleukin-8 (IL-8), melanoma growth-stimulatory activity, and neutrophil-activating peptide selectively mediate priming of the neutrophil NADPH oxidase through the type A or type B IL-8 receptor. Green, S.P., Chuntharapai, A., Curnutte, J.T. J. Biol. Chem. (1996) [Pubmed]
  18. Isolation of the CXC chemokines ENA-78, GRO alpha and GRO gamma from tumor cells and leukocytes reveals NH2-terminal heterogeneity. Functional comparison of different natural isoforms. Wuyts, A., Govaerts, C., Struyf, S., Lenaerts, J.P., Put, W., Conings, R., Proost, P., Van Damme, J. Eur. J. Biochem. (1999) [Pubmed]
  19. Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis. Koch, A.E., Kunkel, S.L., Harlow, L.A., Mazarakis, D.D., Haines, G.K., Burdick, M.D., Pope, R.M., Walz, A., Strieter, R.M. J. Clin. Invest. (1994) [Pubmed]
  20. Folic acid treatment reduces chemokine release from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. Holven, K.B., Aukrust, P., Holm, T., Ose, L., Nenseter, M.S. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  21. The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA. Strieter, R.M., Kunkel, S.L., Burdick, M.D., Lincoln, P.M., Walz, A. Immunol. Invest. (1992) [Pubmed]
  22. 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]
  23. Rhinovirus induction of the CXC chemokine epithelial-neutrophil activating peptide-78 in bronchial epithelium. Donninger, H., Glashoff, R., Haitchi, H.M., Syce, J.A., Ghildyal, R., van Rensburg, E., Bardin, P.G. J. Infect. Dis. (2003) [Pubmed]
  24. Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion. Imaizumi, T., Albertine, K.H., Jicha, D.L., McIntyre, T.M., Prescott, S.M., Zimmerman, G.A. Am. J. Respir. Cell Mol. Biol. (1997) [Pubmed]
  25. Regulation of interleukin-1beta-induced chemokine production and matrix metalloproteinase 2 activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts. Ahmed, S., Pakozdi, A., Koch, A.E. Arthritis Rheum. (2006) [Pubmed]
  26. Biologically active neutrophil chemokine pattern in tonsillitis. Rudack, C., Jörg, S., Sachse, F. Clin. Exp. Immunol. (2004) [Pubmed]
  27. Global effect of PEG-IFN-alpha and ribavirin on gene expression in PBMC in vitro. Taylor, M.W., Grosse, W.M., Schaley, J.E., Sanda, C., Wu, X., Chien, S.C., Smith, F., Wu, T.G., Stephens, M., Ferris, M.W., McClintick, J.N., Jerome, R.E., Edenberg, H.J. J. Interferon Cytokine Res. (2004) [Pubmed]
  28. The level of chemokine CXCL5 in the cerebrospinal fluid is increased during the first 24 hours of ischaemic stroke and correlates with the size of early brain damage. Zaremba, J., Skrobański, P., Losy, J. Folia Morphol. (Warsz) (2006) [Pubmed]
  29. Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils. Luu, N.T., Rainger, G.E., Nash, G.B. J. Immunol. (2000) [Pubmed]
  30. Circulating granulocyte colony-stimulating factor, C-X-C, and C-C chemokines in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome. Proulx, F., Toledano, B., Phan, V., Clermont, M.J., Mariscalco, M.M., Seidman, E.G. Pediatr. Res. (2002) [Pubmed]
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