A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA

被引:193
作者
Ridley, SH [1 ]
Dean, JLE [1 ]
Sarsfield, SJ [1 ]
Brook, M [1 ]
Clark, AR [1 ]
Saklatvala, J [1 ]
机构
[1] Kennedy Inst Rheumatol, London W6 8LH, England
基金
英国医学研究理事会;
关键词
p38 MAP kinase; interleukin-1; cyclooxygenase-2; mRNA stability;
D O I
10.1016/S0014-5793(98)01342-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanism by which p38 mitogen-activated protein kinase (MAPK) regulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells, SE 203580, an inhibitor of p38 MAPK, in the range 0.1-1 mu M inhibited IL-1-stimulated PGE(2) (but not arachidonic acid) release and this was associated with inhibition of induction of COX-2 protein and mRNA, IL-1 stimulated COX-2 transcription in HeLa cells about 2-fold as judged by both reporter gene and nuclear run-on assays. The inhibitor had no significant effect on this. However, in cells previously stimulated with IL-1 it caused rapid destabilisation of COX-2 mRNA independently of on-going transcription. The results suggest a novel function for p38 MAPK in the regulation of mRNA stability, (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:75 / 80
页数:6
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