CCL8

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Entrez
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Chemokine (C-C motif) ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.[1][2]

CCL8 is a small cytokine belonging to the CC chemokine family. The CCL8 protein is produced as a precursor containing 109 amino acids, which is cleaved to produce mature CCL8 containing 75 amino acids. The gene for CCL8 is encoded by 3 exons and is located within a large cluster of CC chemokines on chromosome 17q11.2 in humans.[2][3] MCP-2 is chemotactic for and activates many different immune cells, including mast cells, eosinophils and basophils, (that are implicated in allergic responses), and monocytes, T cells, and NK cells that are involved in the inflammatory response.[4][5] CCL8 elicits its effects by binding to several different cell surface receptors called chemokine receptors. These receptors include CCR1, CCR2B, CCR3 and CCR5.[5][6]

CCL8 is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. CCL8 is a potent inhibitor of HIV1 by virtue of its high-affinity binding to the receptor CCR5, one of the major co-receptors for HIV1.[7] In addition, CCL8 attributes to the growth of metastasis in breast cancer cells. The manipulation of this chemokine activity influences the histology of tumors promoting steps of metastatic processes.[8] CCL8 is also involved in attracting macrophages to the decidua in labor.[9]

References

  1. "Entrez Gene: chemokine (C-C motif) ligand 8".
  2. 2.0 2.1 Van Coillie E, Fiten P, Nomiyama H, Sakaki Y, Miura R, Yoshie O, Van Damme J, Opdenakker G (March 1997). "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2". Genomics. 40 (2): 323–31. doi:10.1006/geno.1996.4594. PMID 9119400.
  3. Van Damme J, Proost P, Lenaerts JP, Opdenakker G (July 1992). "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family". J. Exp. Med. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.
  4. Proost P, Wuyts A, Van Damme J (January 1996). "Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1". J. Leukoc. Biol. 59 (1): 67–74. PMID 8558070.
  5. 5.0 5.1 Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM (February 1998). "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". J. Biol. Chem. 273 (8): 4289–92. doi:10.1074/jbc.273.8.4289. PMID 9468473.
  6. Ge B, Li J, Wei Z, Sun T, Song Y, Khan NU (2017). "Functional expression of CCL8 and its interaction with chemokine receptor CCR3". BMC Immunol. 18: 54. doi:10.1186/s12865-017-0237-5. PMC 5745793. PMID 29281969.
  7. PDB: 1ESR​; Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X (November 2000). "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors". Biochemistry. 39 (46): 14075–81. doi:10.1021/bi0009340. PMID 11087354.
  8. Farmaki E, Chatzistamou I, Kaza V, Kiaris H (2016). "A CCL8 gradient drives breast cancer cell dissemination". Oncogene. 35: 6309–6318. doi:10.1038/onc.2016.161. PMC 5112152. PMID 27181207.
  9. Hamilton SA, Tower CL, Jones RL (2013). "Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour". PLoS One. 8: e56946. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.

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