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

Research output: Contribution to journalArticle

Authors

  • Simon H. Ridley
  • Jonathon L.e. Dean
  • Simon J. Sarsfield
  • Matthew Brook
  • Jeremy Saklatvala

Colleges, School and Institutes

External organisations

  • Kennedy Institute of Rheumatology

Abstract

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. SB 203580, an inhibitor of p38 MAPK, in the range 0.1-1 μM inhibited IL-1-stimulated PGE2 (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. Copyright (C) 1998 Federation of European Biochemical Societies.

Details

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalFEBS Letters
Volume439
Issue number1-2
Publication statusPublished - 13 Nov 1998

Keywords

  • Cyclooxygenase-2, Interleukin-1, mRNA stability, p38 MAP kinase