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

Simon H. Ridley, Jonathon L.e. Dean, Simon J. Sarsfield, Matthew Brook, Andrew R. Clark, Jeremy Saklatvala*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

199 Citations (Scopus)

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.

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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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