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

Journal article

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.

Authors: Ridley, S; Dean, J; Sarsfield, S; Brook, M; Clark, A

• Journal: FEBS letters
• Volume: 439
• Issue: 1-2
• Pages: 75-80
• Publication date: 1998-11-01
• DOI: 10.1016/s0014-5793(98)01342-8
• EISSN: 1873-3468
• ISSN: 0014-5793
• Language: English
• Keywords: Calcium-Calmodulin-Dependent Protein Kinases; Hela Cells; Prostaglandin-Endoperoxide Synthases; p38 Mitogen-Activated Protein Kinases; Imidazoles; Pyridines; Enzyme Inhibitors; Isoenzymes; Dinoprostone; Enzyme Induction; Arachidonic Acids; Cyclooxygenase 2; Membrane Proteins; Mitogen-Activated Protein Kinases; RNA, Messenger; Interleukin-1; Humans; JNK Mitogen-Activated Protein Kinases