炎症反应Toll信号传导通路.pdfVIP

Chinese Journal of Patho hysiology 2000, 16( 6) : 567 567 [ ] 1000- 4718(2000) 06- 0567- 06 Toll 王伯瑶, 黄 宁, 吴 琦 ( , 610041) Toll receptor signaling pathway in inflammation WANG Bo- yao, HUANG Ning, WU Qi (Research Unit of Inf ection Immunity , Dep artment of Pathop hysiology , West China University of Medical Sciences, Chengdu 610041, China A Review Toll signaling athway may lay a curcial role in induction of inflammation- associat ed gene activation. Originally, the Toll/ s aetzle/ Cactus- Dorsal signaling athway is established in the Droso hila embryonic develo ment. Recently, the Toll signaling athway in adult Droso hila has been es tablished in the induction of antimicrobial e tide ex ression. Five humanToll- like rece tor genes ( hTlr l - 5) and one mouse Toll- like rece tor gene ( mTlr - 4) have been isolated. Toll andToll- like rece tor genes encoded molecules are transmembrane roteins with an extracellular leucine re eat domain and a cyto lasmic domain homologous to IL- 1 rece tors. The intracellular signaling cascade involves Tube, Pelle, and Cactus- Dorsal com lex in Droso hila, and MyD88, IRAK, TRAF 6, NIK, - I B kinase, and I B - NFB com lex in mammals. Dorsal and NFB are transcri tion factors, while Cactus and IB are their inhibitors. When the inhibitors hos horylated, the nuclear factors are released and move into nu cleus, leading to immune gene activation. It has been shown from in vitro system that Tlr - 4 mediated LPS signaling in human monocytes for ex ression of IL- 1, IL- 6, IL- 8, and costimulator B7- 1which rovides second signal for T cell res onse. Tlr - 2 can also mediate LPS signaling in human monocytes, leadin