CCL8 explained

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]

Further reading

• Struyf S, Proost P, Vandercappellen J . Synergistic up-regulation of MCP-2/CCL8 activity is counteracted by chemokine cleavage, limiting its inflammatory and anti-tumoral effects. . Eur. J. Immunol. . 39 . 3 . 843–57 . 2009 . 19224633 . 10.1002/eji.200838660 . 41872921 . etal.
• Rom S, Rom I, Passiatore G . CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells. . FASEB J. . 24 . 7 . 2292–300 . 2010 . 20181935 . 10.1096/fj.09-143503 . free . 2887261. etal.
• Menon R, Pearce B, Velez DR . Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants. . Reprod. Biol. Endocrinol. . 7 . 62 . 2009 . 19527514 . 10.1186/1477-7827-7-62 . 2714850. etal . free .
• Segat L, Brandão LA, Guimarães RL . Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment. . Vaccine . 28 . 10 . 2201–6 . 2010 . 20056178 . 10.1016/j.vaccine.2009.12.056 . etal. free .
• Rajaraman P, Brenner AV, Butler MA . Common variation in genes related to innate immunity and risk of adult glioma. . Cancer Epidemiol. Biomarkers Prev. . 18 . 5 . 1651–8 . 2009 . 19423540 . 10.1158/1055-9965.EPI-08-1041 . 2771723. etal.
• Han S, Lan Q, Park AK . Polymorphisms in innate immunity genes and risk of childhood leukemia. . Hum. Immunol. . 71 . 7 . 727–30 . 2010 . 20438785 . 10.1016/j.humimm.2010.04.004 . 2967770. etal.
• Velez DR, Fortunato SJ, Thorsen P . Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. . PLOS ONE . 3 . 9 . e3283 . 2008 . 18818748 . 10.1371/journal.pone.0003283 . 2553267. 2008PLoSO...3.3283V . etal. free .
• Villa C, Venturelli E, Fenoglio C . CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration. . J. Neurol. . 256 . 8 . 1379–81 . 2009 . 19415413 . 10.1007/s00415-009-5138-y . 3147096 . etal.
• Siezen CL, Bont L, Hodemaekers HM . Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes. . Pediatr. Infect. Dis. J. . 28 . 4 . 333–5 . 2009 . 19258923 . 10.1097/INF.0b013e31818e2aa9 . 25601837 . etal. free .
• Vyshkina T, Sylvester A, Sadiq S . CCL genes in multiple sclerosis and systemic lupus erythematosus. . J. Neuroimmunol. . 200 . 1–2 . 145–52 . 2008 . 18602166 . 10.1016/j.jneuroim.2008.05.016 . etal. 5301077 .
• Ruhwald M, Bodmer T, Maier C . Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis. . Eur. Respir. J. . 32 . 6 . 1607–15 . 2008 . 18684849 . 10.1183/09031936.00055508 . etal. free .
• Skibola CF, Bracci PM, Halperin E . Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma. . PLOS ONE . 3 . 7 . e2816 . 2008 . 18636124 . 10.1371/journal.pone.0002816 . 2474696. 2008PLoSO...3.2816S . etal. free .
• Ockinger J, Stridh P, Beyeen AD . Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis. . Genes Immun. . 11 . 2 . 142–54 . 2010 . 19865101 . 10.1038/gene.2009.82 . etal. free .
• Rajaraman P, Brenner AV, Neta G . Risk of meningioma and common variation in genes related to innate immunity. . Cancer Epidemiol. Biomarkers Prev. . 19 . 5 . 1356–61 . 2010 . 20406964 . 10.1158/1055-9965.EPI-09-1151 . 3169167. etal.
• Velez DR, Fortunato S, Thorsen P . Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants. . Am. J. Obstet. Gynecol. . 200 . 2 . 209.e1–27 . 2009 . 19019335 . 10.1016/j.ajog.2008.08.051 . etal. 4829203 .
• Dean RA, Cox JH, Bellac CL . Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx. . Blood . 112 . 8 . 3455–64 . 2008 . 18660381 . 10.1182/blood-2007-12-129080 . etal. free .
• Hori T, Naishiro Y, Sohma H . CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease. . Blood . 111 . 8 . 4403–12 . 2008 . 18256320 . 10.1182/blood-2007-06-097287 . 2288733. etal.
• Schuurhof A, Bont L, Siezen CL . Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls. . Pediatr. Pulmonol. . 45 . 6 . 608–13 . 2010 . 20503287 . 10.1002/ppul.21229 . 24678182 . etal.

Notes and References

1. Web site: Entrez Gene: chemokine (C-C motif) ligand 8.
2. Van Coillie E, Fiten P, Nomiyama H, Sakaki Y, Miura R, Yoshie O, Van Damme J, Opdenakker G . 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 . March 1997 . 9119400 . 10.1006/geno.1996.4594 .
3. Van Damme J, Proost P, Lenaerts JP, Opdenakker G . 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 . July 1992 . 1613466 . 2119277 . 10.1084/jem.176.1.59.
4. Proost P, Wuyts A, Van Damme J . Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1 . J. Leukoc. Biol. . 59 . 1 . 67–74 . January 1996 . 8558070 . 10.1002/jlb.59.1.67. 30445255 .
5. Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM . Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication . J. Biol. Chem. . 273 . 8 . 4289–92 . February 1998 . 9468473 . 10.1074/jbc.273.8.4289. free .
6. 29281969 . 10.1186/s12865-017-0237-5 . 18 . Functional expression of CCL8 and its interaction with chemokine receptor CCR3 . 5745793 . 2017 . BMC Immunol . 54 . Ge B, Li J, Wei Z, Sun T, Song Y, Khan NU. 1 . free .

7. Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X . Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors . Biochemistry . 39 . 46 . 14075–81 . November 2000 . 11087354 . 10.1021/bi0009340.

8. 5112152 . 27181207 . 10.1038/onc.2016.161 . 35 . A CCL8 gradient drives breast cancer cell dissemination . 2016 . Oncogene . 6309–6318 . Farmaki E, Chatzistamou I, Kaza V, Kiaris H. 49 .
9. 23451115 . 10.1371/journal.pone.0056946 . 8 . Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour . 3579936 . 2013 . PLOS ONE . e56946 . Hamilton SA, Tower CL, Jones RL. 2 . 2013PLoSO...856946H . free .