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

Robert Newton, David A. Stevens, Lorraine A. Hart, Mark Lindsay, Ian M. Adcock, Peter J. Barnes

Research output: Contribution to journalArticlepeer-review

103 Citations (SciVal)

Abstract

Many primary response genes, including cyclooxy-genase-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.

Original languageEnglish
Pages (from-to)135-138
Number of pages4
JournalFEBS Letters
Volume418
Issue number1-2
DOIs
Publication statusPublished - 24 Nov 1997

Keywords

  • Cycloheximide
  • Cyclooxygenase
  • Jun N-terminal kinase
  • Nuclear factor-κB
  • Prostaglandin G/H synthase
  • Superinduction

ASJC Scopus subject areas

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

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