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

FEBS Letters

Saklatvala, Jeremy¹  Sarsfield, Simon J.¹  Clark, Andrew R.¹  Brook, Matthew¹  Dean, Jonathon L.E.¹  Ridley, Simon H.¹ 

[1] Kennedy Institute of Rheumatology, 1 Aspenlea Road, London W6 8LH, UK

关键词: p38 MAP kinase;    Interleukin-1;    Cyclooxygenase-2;    mRNA stability;    AA;    arachidonic acid;    COX;    cyclooxygenase;    IL;    interleukin;    JNK;    c-Jun NH2-terminal kinase;    MAPK;    mitogen-activated protein kinase;    PG;    prostaglandin;   

DOI  :  10.1016/S0014-5793(98)01342-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown