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

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

作者机构：Institute of Clinical Pharmacology Anhui Medical University Key Laboratory of Anti-inflammatory and Immuno-pharmacology in Anhui Province Key Laboratory of Research & Development of Chinese Medicine in Anhui Province Hefei Anhui 230032 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2008年第121卷第22期

页      面：2278-2283页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：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）. 

主　　题：arthritis signaling cross-talk G protein MAP kinases 

摘      要：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 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, rlL-la improved the expression of Gi, p-ERK1/2 and p-MEK1/2, cAMP and PKA increased with stimulation of rlL-1α. U0126 inhibited Gi, cAMP and PKA of synoviocytes stimulated by rlL-la. 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.