摘要
Obejctives To study mitogen activated protein kinase (MAPKs) activation in fibroblast like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL 1β, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs Methods Primary cultures of RA FLS were used Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL 1β at various doses, and over different periods Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL 1β Results IL 1β transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK 2, JNK 2 and P 38 ) in RA FLS There was no obvious difference in MAPKs activation among different doses of IL 1β (1?IU/ml,10?IU/ml, 100?IU/ml), but the peak activation of ERK 2, JNK 2 and P 38 took place at 5?min, 15?min and 1?min, respectively, after stimulation with IL 1β The activation of ERK 2 was inhibited by genistein, but the inhibitory role on that of JNK and P 38 was relatively weak Conclusions During signal transduction of IL 1β in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members PTK had a role in the activation of ERK, but had weak effects on that of JNK and P 38
Obejctives To study mitogen activated protein kinase (MAPKs) activation in fibroblast like synoviocytes (FLS) of rheumatoid arthritis (RA) under the stimulation of IL 1β, and to elucidate the role of protein tyrosine kinase (PTK) in the activation of MAPKs Methods Primary cultures of RA FLS were used Western blot was applied to examine transient changes in protein tyrosine phosphorylation status and MAPKs activation in RA FLS stimulated with IL 1β at various doses, and over different periods Genistein, the specific PTK inhibitor, was used to evaluate the inhibitory role in activation of MAPKs by IL 1β Results IL 1β transiently increased protein tyrosine phosphorylation, and activated the MAPKs cascades (mainly ERK 2, JNK 2 and P 38 ) in RA FLS There was no obvious difference in MAPKs activation among different doses of IL 1β (1?IU/ml,10?IU/ml, 100?IU/ml), but the peak activation of ERK 2, JNK 2 and P 38 took place at 5?min, 15?min and 1?min, respectively, after stimulation with IL 1β The activation of ERK 2 was inhibited by genistein, but the inhibitory role on that of JNK and P 38 was relatively weak Conclusions During signal transduction of IL 1β in RA FLS, tyrosine phosphorylation was increased transiently, the MAPKs cascade was activated in a few minutes, and there was heterogenicity in the activation among three subfamily members PTK had a role in the activation of ERK, but had weak effects on that of JNK and P 38
基金
ThestudywassupportedbythegrantfromtheNationalNaturalScienceFundationofChina (No 39730 430 )
