The protein encoded by this gene, CXCL5 is a small cytokine belonging to the CXC chemokine family that is also known as epithelial-derived neutrophil-activating peptide 78 (ENA-78). It is produced following stimulation of cells with the inflammatory cytokines interleukin-1 or tumor necrosis factor-alpha.[3] Expression of CXCL5 has also been observed in eosinophils, and can be inhibited with the type II interferonIFN-γ.[4] This chemokine stimulates the chemotaxis of neutrophils possessing angiogenic properties. It elicits these effects by interacting with the cell surface chemokine receptorCXCR2.[4] The gene for CXCL5 is encoded on four exons and is located on human chromosome 4 amongst several other CXC chemokine genes.[3][5] CXCL5 has been implicated in connective tissue remodelling.[4] CXCL5 has been also described to regulate neutrophil homeostasis.[6]
Clinical significance
CXCL5 plays a role in reducing sensitivity to sunburn pain in some subjects, and is a "potential target which can be utilized to understand more about pain in other inflammatory conditions like arthritis and cystitis.".[7] CXCL5 is well known to have chemotactic and activating functions on neutrophil, mainly during acute inflammatory responses. However CXCL5 expression is also higher in atherosclerosis (a chronic inflammatory condition) but is not associated with neutrophil infiltration. Instead CXCL5 has a protective role in atherosclerosis by directly controlling macrophage foam cell formation.[8]
References
↑Chang MS, McNinch J, Basu R, Simonet S (Nov 1994). "Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene". J Biol Chem. 269 (41): 25277–82. PMID7929219.
↑ 4.04.14.2Persson T, Monsef N, Andersson P, Bjartell A, Malm J, Calafat J, Egesten A (2003). "Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils". Clin. Exp. Allergy. 33 (4): 531–7. doi:10.1046/j.1365-2222.2003.01609.x. PMID12680872.
↑O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet. Cell Genet. 84 (1–2): 39–42. doi:10.1159/000015209. PMID10343098.
Walz A, Schmutz P, Mueller C, Schnyder-Candrian S (1997). "Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease". J. Leukoc. Biol. 62 (5): 604–11. PMID9365115.
Power CA, Furness RB, Brawand C, Wells TN (1995). "Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78 from human platelets". Gene. 151 (1–2): 333–4. doi:10.1016/0378-1119(94)90682-3. PMID7828901.
Corbett MS, Schmitt I, Riess O, Walz A (1995). "Characterization of the gene for human neutrophil-activating peptide 78 (ENA-78)". Biochem. Biophys. Res. Commun. 205 (1): 612–7. doi:10.1006/bbrc.1994.2709. PMID7999089.
Power CA, Clemetson JM, Clemetson KJ, Wells TN (1996). "Chemokine and chemokine receptor mRNA expression in human platelets". Cytokine. 7 (6): 479–82. doi:10.1006/cyto.1995.0065. PMID8580362.
Ahuja SK, Murphy PM (1996). "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". J. Biol. Chem. 271 (34): 20545–50. doi:10.1074/jbc.271.34.20545. PMID8702798.
Keates S, Keates AC, Mizoguchi E, et al. (1997). "Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis". Am. J. Physiol. 273 (1 Pt 1): G75–82. PMID9252512.
Wuyts A, Proost P, Lenaerts JP, et al. (1998). "Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78". Eur. J. Biochem. 255 (1): 67–73. doi:10.1046/j.1432-1327.1998.2550067.x. PMID9692902.
Wyrick PB, Knight ST, Paul TR, et al. (1999). "Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis". J. Infect. Dis. 179 (4): 954–66. doi:10.1086/314676. PMID10068592.
Wuyts A, Govaerts C, Struyf S, et al. (1999). "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". Eur. J. Biochem. 260 (2): 421–9. doi:10.1046/j.1432-1327.1999.00166.x. PMID10095777.
Hogaboam CM, Bone-Larson CL, Steinhauser ML, et al. (1999). "Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines". FASEB J. 13 (12): 1565–74. PMID10463948.
Luu NT, Rainger GE, Nash GB (2000). "Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils". J. Immunol. 164 (11): 5961–9. doi:10.4049/jimmunol.164.11.5961. PMID10820279.