Recent Publication

Counter-regulation mechanism of IL-4 and IFN-α signal transduction thr…

페이지 정보

작성자 관리자 댓글 0건 조회 1,268회 작성일 14-04-07 02:04

본문

Untitled document

http://onlinelibrary.wiley.com/doi/10.1002/eji.201040668/abstract;jsessionid=BA69C3015B3C072F7C139E3A82487BFD.f03t03

 

Abstract

 

IFN-α and IL-4 induce Th1 and Th2 responses, respectively, and often display antagonistic actions against each other. To elucidate the molecular mechanism of counter-regulation, we have investigated the signal interception by IFN-α and IL-4, employing a human B-cell line Ramos, sensitive to both cytokines. In these cells, IFN-α effectively inhibited IL-4-induced Fc epsilon receptor II (CD23) expression, whereas IL-4 suppressed IFN-α-mediated IRF7 expression. The counter-regulatory action by IL-4 and IFN-α proceeded with a delayed kinetics requiring 4 h. Notably, IFN-α did not affect the IL-4-induced tyrosine phosphorylation of STAT6, but induced a time-dependent cytoplasmic accumulation of phosphotyrosine(pY)-STAT6 and a corresponding decrease in nuclear pY-STAT6. By confocal analysis and co-immunoprecipitation assays, we demonstrated the colocalization and molecular interaction of IL-4-induced pY-STAT6 with IFN-α-induced pY-STAT2:p48 in the cytosol. In addition, the over-expression of STAT2 or STAT6 induced the concomitant cytosolic accumulation of pY-STAT6 or pY-STAT2, leading to the suppression of IL-4-induced CD23 or IFN-α-induced IRF7 gene expression, respectively. Our data suggest that the signals ensued by IFN-α and IL-4 induce cytoplasmic sequestration of IL-4-activated STAT6 and IFN-α-activated STAT2:p48 in B cells through the formation of pY-STAT6:pY-STAT2:p48 complex, which provides a novel mechanism by which IFN-α and IL-4 cross-regulate their signaling into the nucleus.

댓글목록

등록된 댓글이 없습니다.

Copyright 2021 © Designed by LHS, ALL RIGHT RESERVED