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Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

ZHANG Ling-ling WEI Wei WANG Qing-tong CHEN Jing-yu CHEN Yin

中华医学杂志(英文版)2008,Vol.121Issue(22):2278-2283,6.
中华医学杂志(英文版)2008,Vol.121Issue(22):2278-2283,6.

Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats

ZHANG Ling-ling 1WEI Wei 1WANG Qing-tong 1CHEN Jing-yu 1CHEN Yin1

作者信息

  • 1. Key Laboratory of Research & Development of Chinese Medicine in Anhui Province,Hefei,Anhui 230032,China
  • 折叠

摘要

Abstract

Background Signaling pathways that regulate the production of cytokines and destructive enzymes have been implicated in rheumatoid arthritis (RA) pathogenesis.There are co-relations between signaling pathways.The aim of this study was to investigate interactions and cross-talks between MEK1/2-extracellular signal-related kinase (ERK1/2)signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis (CIA) rats by the stimulation of interleukin-1 (IL-1),U0126,isoprenaline hydrochloride and aminophyline respectively.Methods Twenty Sprague-Dawley (SD) rats were induced by chicken type Ⅱ collagen.Synoviocytes of CIA rats were isolated and cultured.The expressions of Gi,phosphorylated MEK1/2 (p-MEK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting.cAMP level and protein kinase A (PKA) activity were measured by radioimmunoassay and kinase-glo(R) luminescent kinase assay respectively.Results There was remarkable inflammation in CIA rats accompanied by swelling paws,hyperplastic synovium,pannus and cartilage erosion,cAMP level and PKA activity of synoviocytes decreased.Gi,p-ERK1/2 and p-MEK1/2 increased,rIL-1α improved the expression of Gi,p-ERK1/2 and p-MEK1/2,cAMP and PKA increased with stimulation of rIL-1α.U0126 inhibited Gi,cAMP and PKA of synoviocytes stimulated by rIL-1α.Isoprenaline hydrochloride enhanced Gi,cAMP and PKA,but had no effects on p-MEK1/2 and p-ERK1/2.Aminophyline increased cAMP and PKA,but inhibited p-MEK1/2 and p-ERK1/2.Conclusions Mitogen-activated protein kinases (MAPKs) and G protein-couple signaling are associated with synovitis.There are cross talks between MAPKs and G protein-couple signaling.The two signaling pathways represent potential therapeutic targets for RA.

关键词

arthritis/signaling/cross-talk/G protein/MAP kinases

Key words

arthritis/signaling/cross-talk/G protein/MAP kinases

分类

医药卫生

引用本文复制引用

ZHANG Ling-ling,WEI Wei,WANG Qing-tong,CHEN Jing-yu,CHEN Yin..Cross-talk between MEK1/2-ERK1/2 signaling and G protein-couple signaling in synoviocytes of collagen-induced arthritis rats[J].中华医学杂志(英文版),2008,121(22):2278-2283,6.

基金项目

This work was supported by the grants from the National Natural Science Foundation of China (No.30572356) and the Natural Science Foundation of the Education Department of Anhui Province (No.KJ2008B295). (No.30572356)

中华医学杂志(英文版)

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