CXCR3
趨化因子受體CXCR3是G蛋白偶連的七跨膜域受體，可選擇性地與CXC趨化因子（CXCL9，CXCL10，和CXCL11）結合[1]。 CXCR3又稱G蛋白偶聯受體9(GPR9)和CD183。有兩種變異的CXCR3受體。CXCR3－A與CXCL9， CXCL10，CXCL11結合；而CXCR3-B除了與CXCL9， CXCL10，CXCL11結合外還可以與CXCL4結合[2]。
表達[編輯]
CXCR3主要表達在T細胞、自然殺傷細胞活性上[3]，有的上皮細胞和一些內皮細胞也表達CXCR3。 I型輔助T細胞（Th1）優先表達CXCR3及CCR5[3]，而II型輔助T細胞（Th2）表達CCR3和CCR4。 CXCR3與配體結合後在誘導I型輔助T細胞（Th1）遷移的同時又阻止II型輔助T細胞（Th2）的遷徙。從而增強T細胞的分化效應。
信號傳遞[編輯]
CXCR3與其配體CXCL9， CXCL10，CXCL11的結合，能引起細胞鈣離子的內流，啟動肌醇磷脂3-激酶和絲裂原活化蛋白激酶（MAPK）[4]。詳細的信號通路尚未確立，但與其他的趨化因子受體的信號傳遞有類似的激酶。
功能[編輯]
CXCR3調節白血球遷徙。CXCR3與配體相互作用引起I型輔助T細胞（Th1）的遷移，並促進I型輔助T細胞（Th1）成熟。
疾病[編輯]
CXCR3可能在下列疾病中起作用，包括動脈粥樣硬化[5]、多發性硬化[6]、肺纖維化[7], I型糖尿病[8]，重症肌無力、急性心臟移植排斥[9]。開發阻斷CXCR3與其配體相互作用的藥物可提供治療這些疾病的新途徑。
參見[編輯]
參考文獻[編輯]
- ^ Clark-Lewis I, Mattioli I, Gong JH, Loetscher P. Structure-function relationship between the human chemokine receptor CXCR3 and its ligands. J Biol Chem. 2003 Jan 3;278(1):289-95.
- ^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003 Jun 2;197(11):1537-49.
- ^ 3.0 3.1 Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998 Feb 15;101(4):746-54.
- ^ Smit MJ, Verdijk P, van der Raaij-Helmer EM, Navis M, Hensbergen PJ, Leurs R, Tensen CP. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood. 2003 Sep 15;102(6):1959-65.
- ^ Mach F, Sauty A, Iarossi AS, Sukhova GK, Neote K, Libby P, Luster AD. Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. J Clin Invest. 1999 Oct;104(8):1041-50.
- ^ Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, Qin S, Rottman J, Sellebjerg F, Strieter RM, Frederiksen JL, Ransohoff RM. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest. 1999 Mar;103(6):807-15.
- ^ Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, Fan J, Gao Y, Yin Z, Homer R, Gerard C, Noble PW. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest. 2004 Jul;114(2):291-9.
- ^ Frigerio S, Junt T, Lu B, Gerard C, Zumsteg U, Hollander GA, Piali L. Beta cells are responsible for CXCR3-mediated T-cell infiltration in insulitis. Nat Med. 2002 Dec;8(12):1414-20.
- ^ Hancock WW, Lu B, Gao W, Csizmadia V, Faia K, King JA, Smiley ST, Ling M, Gerard NP, Gerard C. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med. 2000 Nov 20;192(10):1515-20.
外部連結[編輯]
- Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med. 2006 Feb 9;354(6):610-21.（頁面存檔備份，存於網際網路檔案館）
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