From Wikipedia, the free encyclopedia
Mammalian protein found in Homo sapiens
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 .
[3]
[4]
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 17q 11.2 in humans.
[4]
[5] 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.
[6]
[7] CCL8 elicits its effects by binding to several different cell surface receptors called
chemokine receptors . These receptors include
CCR1 ,
CCR2B ,
CCR3 and
CCR5 .
[7]
[8]
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.
[9] 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.
[10] CCL8 is also involved in attracting macrophages to the decidua in labor.
[11]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000108700 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Entrez Gene: chemokine (C-C motif) ligand 8" .
^
a
b 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 .
^ 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 .
^ 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.
doi :
10.1002/jlb.59.1.67 .
PMID
8558070 .
S2CID
30445255 .
^
a
b 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 .
^ 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 (1): 54.
doi :
10.1186/s12865-017-0237-5 .
PMC
5745793 .
PMID
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^
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 .
^ Farmaki E, Chatzistamou I, Kaza V, Kiaris H (2016).
"A CCL8 gradient drives breast cancer cell dissemination" . Oncogene . 35 (49): 6309–6318.
doi :
10.1038/onc.2016.161 .
PMC
5112152 .
PMID
27181207 .
^ 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 (2): e56946.
Bibcode :
2013PLoSO...856946H .
doi :
10.1371/journal.pone.0056946 .
PMC
3579936 .
PMID
23451115 .
External links
Further reading
Struyf S, Proost P, Vandercappellen J, et al. (2009). "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.
doi :
10.1002/eji.200838660 .
PMID
19224633 .
S2CID
41872921 .
Rom S, Rom I, Passiatore G, et al. (2010).
"CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells" . FASEB J . 24 (7): 2292–300.
doi :
10.1096/fj.09-143503 .
PMC
2887261 .
PMID
20181935 .
Menon R, Pearce B, Velez DR, et al. (2009).
"Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants" . Reprod. Biol. Endocrinol . 7 : 62.
doi :
10.1186/1477-7827-7-62 .
PMC
2714850 .
PMID
19527514 .
Segat L, Brandão LA, Guimarães RL, et al. (2010).
"Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment" . Vaccine . 28 (10): 2201–6.
doi :
10.1016/j.vaccine.2009.12.056 .
PMID
20056178 .
Rajaraman P, Brenner AV, Butler MA, et al. (2009).
"Common variation in genes related to innate immunity and risk of adult glioma" . Cancer Epidemiol. Biomarkers Prev . 18 (5): 1651–8.
doi :
10.1158/1055-9965.EPI-08-1041 .
PMC
2771723 .
PMID
19423540 .
Han S, Lan Q, Park AK, et al. (2010).
"Polymorphisms in innate immunity genes and risk of childhood leukemia" . Hum. Immunol . 71 (7): 727–30.
doi :
10.1016/j.humimm.2010.04.004 .
PMC
2967770 .
PMID
20438785 .
Velez DR, Fortunato SJ, Thorsen P, et al. (2008).
"Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants" . PLOS ONE . 3 (9): e3283.
Bibcode :
2008PLoSO...3.3283V .
doi :
10.1371/journal.pone.0003283 .
PMC
2553267 .
PMID
18818748 .
Villa C, Venturelli E, Fenoglio C, et al. (2009). "CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration". J. Neurol . 256 (8): 1379–81.
doi :
10.1007/s00415-009-5138-y .
PMID
19415413 .
S2CID
3147096 .
Siezen CL, Bont L, Hodemaekers HM, et al. (2009).
"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.
doi :
10.1097/INF.0b013e31818e2aa9 .
PMID
19258923 .
S2CID
25601837 .
Vyshkina T, Sylvester A, Sadiq S, et al. (2008).
"CCL genes in multiple sclerosis and systemic lupus erythematosus" . J. Neuroimmunol . 200 (1–2): 145–52.
doi :
10.1016/j.jneuroim.2008.05.016 .
PMC
5301077 .
PMID
18602166 .
Ruhwald M, Bodmer T, Maier C, et al. (2008).
"Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis" . Eur. Respir. J . 32 (6): 1607–15.
doi :
10.1183/09031936.00055508 .
PMID
18684849 .
Skibola CF, Bracci PM, Halperin E, et al. (2008).
"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.
Bibcode :
2008PLoSO...3.2816S .
doi :
10.1371/journal.pone.0002816 .
PMC
2474696 .
PMID
18636124 .
Ockinger J, Stridh P, Beyeen AD, et al. (2010).
"Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis" . Genes Immun . 11 (2): 142–54.
doi :
10.1038/gene.2009.82 .
PMID
19865101 .
Xie Z, Zhang J, Wu J, et al. (2008).
"Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes" . Diabetes . 57 (12): 3222–30.
doi :
10.2337/db08-0610 .
PMC
2584127 .
PMID
18835932 .
Rajaraman P, Brenner AV, Neta G, et al. (2010).
"Risk of meningioma and common variation in genes related to innate immunity" . Cancer Epidemiol. Biomarkers Prev . 19 (5): 1356–61.
doi :
10.1158/1055-9965.EPI-09-1151 .
PMC
3169167 .
PMID
20406964 .
Velez DR, Fortunato S, Thorsen P, et al. (2009).
"Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants" . Am. J. Obstet. Gynecol . 200 (2): 209.e1–27.
doi :
10.1016/j.ajog.2008.08.051 .
PMC
4829203 .
PMID
19019335 .
Dean RA, Cox JH, Bellac CL, et al. (2008).
"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.
doi :
10.1182/blood-2007-12-129080 .
PMID
18660381 .
Hori T, Naishiro Y, Sohma H, et al. (2008).
"CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease" . Blood . 111 (8): 4403–12.
doi :
10.1182/blood-2007-06-097287 .
PMC
2288733 .
PMID
18256320 .
Schuurhof A, Bont L, Siezen CL, et al. (2010). "Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls". Pediatr. Pulmonol . 45 (6): 608–13.
doi :
10.1002/ppul.21229 .
PMID
20503287 .
S2CID
24678182 .
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