CCL8
Hemokinski (C-C motivni) ligand 8 (CCL8), znan i kao monocitni hemoatraktantni protein 2 (MCP2), je protein koji je kod ljudi kodiran genom CCL8.[3][4]
CCL8 je mali citokin koji pripada porodici CC hemokina. CCL8 protein se proizvodi kao prekursor koji sadrži 109 aminokiselina, a koji se cijepa da bi se dobio zreli CCL8 koji sadrži 75 aminokiselina. Kod ljudi, gen za CCL8 ima tri egzona i nalazi se unutar velikog skupa CC hemokinskih gena na hromosomu 17 q11.2.[4][5] MCP-2 je hemotaksijski i aktivira mnoge različite imunske ćelije, uključujući mastocite, eozinofile i bazofile (koje su uključene u alergijske reakcije) i monocite, T-ćelije i NK-ćelije koji su uključeni u upalni odgovor.[6][7] Svoje efekte CCL8 izaziva vezanjem na nekoliko različitih receptora na ćelijskoj površini, zvanih hemokinski receptori. Ovi receptori uključuju CCR1, CCR2B, CCR3 i CCR5.[7][8]
CCL8 je CC-hemokin koji koristi više ćelijskih receptora za privlačenje i aktiviranje ljudskih leukocita. CCL8 je snažni inhibitor HIV 1, zahvaljujući visokom afinitetu vezanja za receptor CCR5, jedan od glavnih koreceptora za HIV1.[9] Pored toga, CCL8 –u pripisuje se rast metastaza u ćelijama raka dojke. Manipulacija ovom hemokinskom aktivnošću utiče na histologiju tumora, promovirajući korake metastatskih procesa.[10] CCL8 je također uključen u privlačenje makrofaga u porođajnu deciduu.[11]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 99 aminokiselina, a molekulska težina 11.246 Da.[12]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MKVSAALLCL | LLMAATFSPQ | GLAQPDSVSI | PITCCFNVIN | RKIPIQRLES | ||||
| YTRITNIQCP | KEAVIFKTKR | GKEVCADPKE | RWVRDSMKHL | DQIFQNLKP |
- Simboli
C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000108700 - Ensembl, maj 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 (mart 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 (juli 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 (januar 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 (februar 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 29281969.
- ^ PDB 1ESR; Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X (novembar 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. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.
- ^ "UniProt, P80075". Pristupljeno 27. 6. 2021.
Vanjski linkovi
[uredi | uredi izvor]- Lokacija ljudskog genoma CCL8 i stranica sa detaljima o genu CCL8 u UCSC Genome Browseru.
Dopunska literatura
[uredi | uredi izvor]- 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.
- 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.
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- 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. 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.
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- 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. 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.