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

S H Ridley, J L Dean, S J Sarsfield, M Brook, A R Clark, J Saklatvala

Research output: Contribution to journalArticlepeer-review


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 microM 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.

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


  • Arachidonic Acids
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cyclooxygenase 2
  • Dinoprostone
  • Enzyme Induction
  • Enzyme Inhibitors
  • HeLa Cells
  • Humans
  • Imidazoles
  • Interleukin-1
  • Isoenzymes
  • JNK Mitogen-Activated Protein Kinases
  • Membrane Proteins
  • Mitogen-Activated Protein Kinases
  • Prostaglandin-Endoperoxide Synthases
  • Pyridines
  • RNA, Messenger
  • p38 Mitogen-Activated Protein Kinases


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