Superinduction of COX‐2 mRNA by cycloheximide and interleukin‐1β involves increased transcription and correlates with increased NF‐κB and JNK activation

FEBS Letters

Hart, Lorraine A.¹  Stevens, David A.¹  Adcock, Ian M.¹  Newton, Robert¹  Barnes, Peter J.¹  Lindsay, Mark¹ 

[1] Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY, UK

关键词: Cyclooxygenase;    Prostaglandin G/H synthase;    Superinduction;    Cycloheximide;    Jun N-terminal kinase;    Nuclear factor-κB;    COX;    cyclooxygenase;    CRE;    cAMP responsive element;    EMSA;    electrophoretic mobility shift assay;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;    IL;    interleukin;    JNK;    Jun N-terminal kinase;    NF-κB;    nuclear factor-κB;    PG;    prostaglandin;    RT-PCR;    reverse transcriptase-polymerase chain reaction;    TNFα;    tumour necrosis factor-α;   

DOI  :  10.1016/S0014-5793(97)01362-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Many primary response genes, including cyclooxygenase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1β-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-κB binding to COX-2 promoter κB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-κB by de novo IκBα synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

【 授权许可】

Unknown