CCL7
Hemokinski (C-C motivni) ligand 7 (CCL7) je mali citokin koji se prethodno zvao monocitno-hemotaksijski protein 3 (MCP3). CCL7 je mali protein koji pripada porodici CC- hemokina i najuže je povezan sa CCL2 (prethodno zvanim MCP1).[3]
Aminokiselinska sekvenca
- Dužina polipeptidnog lanca je 99 aminokiselina, a molekulska težina 11.200 Da.[4]
- 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
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MKASAALLCL | LLTAAAFSPQ | GLAQPVGINT | STTCCYRFIN | KKIPKQRLES | ||||
| YRRTTSSHCP | REAVIFKTKL | DKEICADPTQ | KWVQDFMKHL | DKKTQTPKL |
Genomika
[uredi | uredi izvor]U ljudskom genomU, CCL7 je kodiran genom CCL7, koji je jedan od nekoliko gena hemokina grupiranih u hromosomu 17, sekvenca q11.2-q12. Ova regija sadrži gen za MCP podskupinu CC-hemokina. Gen CCL7 dobio je simbol lokusa SCYA7.[5]
Gen sadrži tri egzona i dva introna. Prvi egzon sadrži 5′-neprevedeno područje (5′-UTR), informacije za signalnu sekvencu (23 aminokiseline) i prve dvije aminokiseline zrelog proteina. Drugi egzon kodira aminokiseline 3–42 zrelih proteina. Treći egzon sastoji se od C-terminalne regije proteina, 3′-UTR, koji sadrži jednu ili više destabilizirajućih sekvenci bogatih AU i signal poliadenilacije.[6]
Molekulska biologija
[uredi | uredi izvor]CCL7 je prvo okarakteriziran iz supernatanta osteosarkoma.[7] CCL7 se sastoji od 99 aminokiselina, koje sadrže signalni peptid od 23 aminokiseline. Zreli protein sa oko 76 aminokiselina izlučuje se nakon cijepanja signalnog peptida.[8] Za razliku od većine hemokina, CCL7 postoji u općenitom monomernom obliku, razlikujući se od dimera koji nastaje u visoko koncentriranom rastvoru.[9][10]
U COS ćelijama, CCL7 može postojati u četiri različita glikotipa s molekulskom težinom 11, 13, 17 i 18 kDa.[11]
CCL7 posreduje u efektima na tipove imunskih ćelija, vezujući se za brojne receptore, uključujući CCR1, CCR2, CCR3, CCR5 i CCR10.[8][12] Ovi receptori pripadaju G-protein vezanih sedmo-transmembranskih receptora.[13] CCL7 također može komunicirati sa površinskim ćelijskim glikozaminoglikanima (GAGs) prisutnim na površinama svih životinjskih ćelija.[14]
Funkcija
[uredi | uredi izvor]CCL7 se eksprimira u mnogim tipovima ćelija, uključujući stromske, keratinocitne, ćelije glatkih mišića disajnih puteva, parenhimske ćelije, fibroblaste i bijele krvne ćelije, a također iu tumorskim ćelijama.[6][8][15]
CC7 uglavnom djeluje kao hemoatraktant za nekoliko tipova leukocita, uključujući monocite, eozinofile, bazofile, dendritske ćelije (DC), neutrofile, NK ćelije i aktivirane T-limfocite.[14][16] Kao hemotaksijski faktor, CCL7 regrutuje leukocite u zaražena tkiva kako bi posredovao u imunskom odgovoru.[14] Nadalje, CCL7 ima utjecaj na dijapedezu i ekstravazaciju leukocita.[17] Pozitivan učinak CCL7 uglavnom se uočava u mobilizaciji monocita iz koštane srži u cirkulaciju krvi i u regrutovanju monocita na mjesta upale.[18] Također je izviješteno da CCL7 može inducirati i migraciju neutrofila na mjesto upale, povećavanjem unutarćelijskog fluksa Ca2+, što je uobičajenije za članove porodice CXC hemokina.[19]
Brzina imunskih odgovora varira ovisno o tipu ćelija. U epitelnim ćelijama, fibroblastima i endotelnim ćelijjama, odgovor je neposredan nakon stimulacije proupalnim citokinima, kao što su IL-1β i TNFα. U T-limfocitima, ekspresija CCL7 se javlja 3-5 dana nakon stimulacije.[20]
Dokazano je da CCL7 stupa u interakciju s MMP2, vezanjem CCR2 receptora.[21]
Klinički značaj
[uredi | uredi izvor]CCL7 je multipotentni hemokin, uključen u antibakterijski, antivirusni i antigljivični imunski odgovor. Naprimjer, CCL7-posredovana stimulacija CCR2 hemokinskih receptora na monocitima sudjeluje u uklanjanju infekcija Listeria monocytogenes, regrutovanjem monocita i dendritskih ćelija koje proizvode TNF/iNOS (TipDCs).[22] Uloga CCL7 također je uočena kod miša zaraženog virusom zapadnog Nila. Kod genetički deficitarnih miševa u CCL7-u, povećana je smrtnost, zbog smanjenja monocita i neutrofila.[23] Rano induciranje CCL7 nizvodno od TLR9 signalizacije također promovira razvoj snažne imunosti na kriptokokne infekcije.[24]
Primjećene bolesti povezane sa poremećajem regulacije CCL7. Naprimjer, abnormalno povećanje CCL7 pogoršava mnoge poremećaje, poput HIV-a ili lezijske psorijaze.[25][26] Nadalje, CCL7 je uključen u razne imunske bolesti, kao što su ulcerozni kolitis, multipla skleroza ili neatopijska i atopijska astma.[14][27]
Izgleda da ekspresija CCL7 može aktivirati i antitumorski imunski odgovor.[19]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000108688 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Rollins BJ (august 1997). "Chemokines". Blood. 90 (3): 909–28. PMID 9242519.
- ^ "UniProt, P80098". Pristupljeno June 27, 2021.
- ^ Opdenakker G, Fiten P, Nys G, Froyen G, Van Roy N, Speleman F, et al. (maj 1994). "The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment to the C-C chemokine gene cluster on chromosome 17q11.2-q12". Genomics. 21 (2): 403–8. doi:10.1006/geno.1994.1283. PMID 7916328.
- ^ a b Van Coillie E, Van Damme J, Opdenakker G (mart 1999). "The MCP/eotaxin subfamily of CC chemokines". Cytokine & Growth Factor Reviews. 10 (1): 61–86. doi:10.1016/s1359-6101(99)00005-2. PMID 10379912.
- ^ 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". The Journal of Experimental Medicine. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.
- ^ a b c Liu Y, Cai Y, Liu L, Wu Y, Xiong X (2018). "Crucial biological functions of CCL7 in cancer". PeerJ. 6: e4928. doi:10.7717/peerj.4928. PMC 6004300. PMID 29915688.
- ^ Kim KS, Rajarathnam K, Clark-Lewis I, Sykes BD (oktobar 1996). "Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3". FEBS Letters. 395 (2–3): 277–82. doi:10.1016/0014-5793(96)01024-1. PMID 8898111.
- ^ Meunier S, Bernassau JM, Guillemot JC, Ferrara P, Darbon H (april 1997). "Determination of the three-dimensional structure of CC chemokine monocyte chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy". Biochemistry. 36 (15): 4412–22. doi:10.1021/bi9627929. PMID 9109648.
- ^ Greška kod citiranja: Nevaljana oznaka
<ref>; nije naveden tekst za reference s imenom: 0 - ^ Palomino DC, Marti LC (juli 2015). "Chemokines and immunity". Einstein. 13 (3): 469–73. doi:10.1590/S1679-45082015RB3438. PMC 4943798. PMID 26466066.
- ^ Griffith JW, Sokol CL, Luster AD (2014). "Chemokines and chemokine receptors: positioning cells for host defense and immunity". Annual Review of Immunology. 32: 659–702. doi:10.1146/annurev-immunol-032713-120145. PMID 24655300.
- ^ a b c d Menten P, Wuyts A, Van Damme J (oktobar 2001). "Monocyte chemotactic protein-3". European Cytokine Network. 12 (4): 554–60. PMID 11781181.
- ^ Menten P, Proost P, Struyf S, Van Coillie E, Put W, Lenaerts JP, et al. (februar 1999). "Differential induction of monocyte chemotactic protein-3 in mononuclear leukocytes and fibroblasts by interferon-alpha/beta and interferon-gamma reveals MCP-3 heterogeneity". European Journal of Immunology. 29 (2): 678–85. doi:10.1002/(SICI)1521-4141(199902)29:023.0.CO;2-J. PMID 10064085.
- ^ Ali S, Robertson H, Wain JH, Isaacs JD, Malik G, Kirby JA (juli 2005). "A non-glycosaminoglycan-binding variant of CC chemokine ligand 7 (monocyte chemoattractant protein-3) antagonizes chemokine-mediated inflammation". Journal of Immunology. 175 (2): 1257–66. doi:10.4049/jimmunol.175.2.1257. PMID 16002730.
- ^ Weber KS, von Hundelshausen P, Clark-Lewis I, Weber PC, Weber C (februar 1999). "Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow". European Journal of Immunology. 29 (2): 700–12. doi:10.1002/(SICI)1521-4141(199902)29:023.0.CO;2-1. PMID 10064088.
- ^ Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, Weisberg SP, et al. (april 2007). "Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites". The Journal of Clinical Investigation. 117 (4): 902–9. doi:10.1172/JCI29919. PMC 1810572. PMID 17364026.
- ^ a b Fioretti F, Fradelizi D, Stoppacciaro A, Ramponi S, Ruco L, Minty A, et al. (juli 1998). "Reduced tumorigenicity and augmented leukocyte infiltration after monocyte chemotactic protein-3 (MCP-3) gene transfer: perivascular accumulation of dendritic cells in peritumoral tissue and neutrophil recruitment within the tumor". Journal of Immunology. 161 (1): 342–6. PMID 9647242.
- ^ Song A, Nikolcheva T, Krensky AM (oktobar 2000). "Transcriptional regulation of RANTES expression in T lymphocytes". Immunological Reviews. 177: 236–45. doi:10.1034/j.1600-065x.2000.17610.x. PMID 11138780.
- ^ Opdenakker G, Froyen G, Fiten P, Proost P, Van Damme J (mart 1993). "Human monocyte chemotactic protein-3 (MCP-3): molecular cloning of the cDNA and comparison with other chemokines". Biochemical and Biophysical Research Communications. 191 (2): 535–42. doi:10.1006/bbrc.1993.1251. PMID 8461011.
- ^ Serbina NV, Shi C, Pamer EG (2012). "Monocyte-mediated immune defense against murine Listeria monocytogenes infection". Advances in Immunology. 113: 119–34. doi:10.1016/B978-0-12-394590-7.00003-8. PMC 3985089. PMID 22244581.
- ^ Bardina SV, Michlmayr D, Hoffman KW, Obara CJ, Sum J, Charo IF, et al. (novembar 2015). "Differential Roles of Chemokines CCL2 and CCL7 in Monocytosis and Leukocyte Migration during West Nile Virus Infection". Journal of Immunology. 195 (9): 4306–18. doi:10.4049/jimmunol.1500352. PMC 4610864. PMID 26401006.
- ^ Ouchi N, Parker JL, Lugus JJ, Walsh K (februar 2011). "Adipokines in inflammation and metabolic disease". Nature Reviews. Immunology. 11 (2): 85–97. doi:10.1038/nri2921. PMC 3518031. PMID 21252989.
- ^ Atluri VS, Pilakka-Kanthikeel S, Garcia G, Jayant RD, Sagar V, Samikkannu T, et al. (juni 2016). "Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages". Scientific Reports. 6: 27864. doi:10.1038/srep27864. PMC 4913267. PMID 27321752.
- ^ Brunner PM, Glitzner E, Reininger B, Klein I, Stary G, Mildner M, et al. (juli 2015). "CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin". Experimental Dermatology. 24 (7): 522–8. doi:10.1111/exd.12709. PMID 25828150.
- ^ Romagnani S (maj 2002). "Cytokines and chemoattractants in allergic inflammation". Molecular Immunology. 38 (12–13): 881–5. doi:10.1016/s0161-5890(02)00013-5. PMID 12009564.
Dopunska literatura
[uredi | uredi izvor]- Menten P, Wuyts A, Van Damme J (2002). "Monocyte chemotactic protein-3". European Cytokine Network. 12 (4): 554–60. PMID 11781181.
- 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". The Journal of Experimental Medicine. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.
- Ben-Baruch A, Xu L, Young PR, Bengali K, Oppenheim JJ, Wang JM (septembar 1995). "Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3". The Journal of Biological Chemistry. 270 (38): 22123–8. doi:10.1074/jbc.270.38.22123. PMID 7545673.
- Opdenakker G, Fiten P, Nys G, Froyen G, Van Roy N, Speleman F, et al. (maj 1994). "The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment to the C-C chemokine gene cluster on chromosome 17q11.2-q12". Genomics. 21 (2): 403–8. doi:10.1006/geno.1994.1283. PMID 7916328.
- Minty A, Chalon P, Guillemot JC, Kaghad M, Liauzun P, Magazin M, et al. (1993). "Molecular cloning of the MCP-3 chemokine gene and regulation of its expression". European Cytokine Network. 4 (2): 99–110. PMID 8318676.
- Opdenakker G, Froyen G, Fiten P, Proost P, Van Damme J (mart 1993). "Human monocyte chemotactic protein-3 (MCP-3): molecular cloning of the cDNA and comparison with other chemokines". Biochemical and Biophysical Research Communications. 191 (2): 535–42. doi:10.1006/bbrc.1993.1251. PMID 8461011.
- Combadiere C, Ahuja SK, Van Damme J, Tiffany HL, Gao JL, Murphy PM (decembar 1995). "Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B". The Journal of Biological Chemistry. 270 (50): 29671–5. doi:10.1074/jbc.270.50.29671. PMID 8530354.
- Power CA, Clemetson JM, Clemetson KJ, Wells TN (august 1995). "Chemokine and chemokine receptor mRNA expression in human platelets". Cytokine. 7 (6): 479–82. doi:10.1006/cyto.1995.0065. PMID 8580362.
- Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS (maj 1996). "Cloning, expression, and characterization of the human eosinophil eotaxin receptor". The Journal of Experimental Medicine. 183 (5): 2349–54. doi:10.1084/jem.183.5.2349. PMC 2192548. PMID 8642344.
- Kim KS, Rajarathnam K, Clark-Lewis I, Sykes BD (oktobar 1996). "Structural characterization of a monomeric chemokine: monocyte chemoattractant protein-3". FEBS Letters. 395 (2–3): 277–82. doi:10.1016/0014-5793(96)01024-1. PMID 8898111. S2CID 24062093.
- Meunier S, Bernassau JM, Guillemot JC, Ferrara P, Darbon H (april 1997). "Determination of the three-dimensional structure of CC chemokine monocyte chemoattractant protein 3 by 1H two-dimensional NMR spectroscopy". Biochemistry. 36 (15): 4412–22. doi:10.1021/bi9627929. PMID 9109648.
- Polentarutti N, Introna M, Sozzani S, Mancinelli R, Mantovani G, Mantovani A (septembar 1997). "Expression of monocyte chemotactic protein-3 in human monocytes and endothelial cells". European Cytokine Network. 8 (3): 271–4. PMID 9346360.
- Bonini JA, Martin SK, Dralyuk F, Roe MW, Philipson LH, Steiner DF (oktobar 1997). "Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3". DNA and Cell Biology. 16 (10): 1249–56. doi:10.1089/dna.1997.16.1249. PMID 9364936.
- Nibbs RJ, Wylie SM, Yang J, Landau NR, Graham GJ (decembar 1997). "Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6". The Journal of Biological Chemistry. 272 (51): 32078–83. doi:10.1074/jbc.272.51.32078. PMID 9405404.
- Wang JM, Ueda H, Howard OM, Grimm MC, Chertov O, Gong X, et al. (oktobar 1998). "HIV-1 envelope gp120 inhibits the monocyte response to chemokines through CD4 signal-dependent chemokine receptor down-regulation". Journal of Immunology. 161 (8): 4309–17. PMID 9780207.
- Albini A, Ferrini S, Benelli R, Sforzini S, Giunciuglio D, Aluigi MG, et al. (oktobar 1998). "HIV-1 Tat protein mimicry of chemokines". Proceedings of the National Academy of Sciences of the United States of America. 95 (22): 13153–8. Bibcode:1998PNAS...9513153A. doi:10.1073/pnas.95.22.13153. PMC 23742. PMID 9789057.
- Rabin RL, Park MK, Liao F, Swofford R, Stephany D, Farber JM (april 1999). "Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling". Journal of Immunology. 162 (7): 3840–50. PMID 10201901.
- Wedemeyer J, Lorentz A, Göke M, Meier PN, Flemming P, Dahinden CA, et al. (maj 1999). "Enhanced production of monocyte chemotactic protein 3 in inflammatory bowel disease mucosa". Gut. 44 (5): 629–35. doi:10.1136/gut.44.5.629. PMC 1727483. PMID 10205198.
- Blanpain C, Migeotte I, Lee B, Vakili J, Doranz BJ, Govaerts C, et al. (septembar 1999). "CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist". Blood. 94 (6): 1899–905. doi:10.1182/blood.V94.6.1899. PMID 10477718.
- Jordan NJ, Kolios G, Abbot SE, Sinai MA, Thompson DA, Petraki K, Westwick J (oktobar 1999). "Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells". The Journal of Clinical Investigation. 104 (8): 1061–9. doi:10.1172/JCI6685. PMC 408573. PMID 10525044.
Vanjski linkovi
[uredi | uredi izvor]- Lokacija ljudskog genoma CCL7 i stranica sa detaljima o genu CCL7 u UCSC Genome Browseru.