Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis
Hs. Lu et al., Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis, CHIN MED J, 113(10), 2000, pp. 872-876
Objectives To study mitogen-activated protein kinase (MAPKs) activation in
fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) under the s
timulation of IL-1 beta, and to elucidate the role of protein tyrosine kina
se (PTK) in the activation of MAPKs.
Methods Primary cultures of RA FLS were used. Western blot was applied to e
xamine transient changes in protein tyrosine phosphorylation status and MAP
Ks activation in RA FLS stimulated with IL-1 beta at various doses, and ove
r different periods. Genistein, the specific PTK inhibitor, was used to eva
luate the inhibitory role in activation of MAPKs by IL-1 beta.
Results IL-1 beta transiently increased protein tyrosine phosphorylation, a
nd activated the MAPKs cascades (mainly ERK2, JNK(2) and P-38) in RA FLS. T
here was no obvious difference in MAPKs activation among different doses of
IL-1 beta (1 IU/ml, 10 IU/ml, 100 IU/ml), but the peak activation of ERK2,
JNK(2) and P-38 took place at 5 min, 15 min and 1 min, respectively, after
stimulation with IL-1 beta. The activation of ERK2 was inhibited by genist
ein, but the inhibitory role on that of JNK and P-38 was relatively weak.
Conclusions During signal transduction of IL-1 beta in RA FLS, tyrosine pho
sphorylation was increased transiently, the MAPKs cascade was activated in
a few minutes, and there was heterogenicity in the activation among three s
ubfamily members. PTK had a role in the activation of ERK, but had weak eff
ects on that of JNK and P-38.