A P38 MAP KINASE INHIBITOR REGULATES STABILITY OF INTERLEUKIN-1-INDUCED CYCLOOXYGENASE-2 MESSENGER-RNA

The mechanism by which p38 mitogen-activated protein kinase (MAPK) reg ulates the induction of cyclooxygenase (COX)-2 by interleukin-1 (IL-1) has been investigated in HeLa cells, SE 203580, an inhibitor of p38 M APK, 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 transcripti on in HeLa cells about 2-fold as judged by both reporter gene and nucl ear run-on assays. The inhibitor had no significant effect on this. Ho wever, in cells previously stimulated with IL-1 it caused rapid destab ilisation of COX-2 mRNA independently of on-going transcription. The r esults suggest a novel function for p38 MAPK in the regulation of mRNA stability, (C) 1998 Federation of European Biochemical Societies.