IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase

FEBS Lett. 2003 Jul 17;547(1-3):75-9. doi: 10.1016/s0014-5793(03)00672-0.

Abstract

Prostaglandin (PG) E2 release is induced in pulmonary A549 cells by the NF-kappaB-activating stimuli interleukin-1beta (IL-1beta) and phorbol 12-myristate 13-acetate (PMA). Adenoviral over-expression of IkappaBalphaDeltaN, a dominant NF-kappaB inhibitor, prevents NF-kappaB-dependent transcription and was used to qualify the role of NF-kappaB in the release of PGE2. IkappaBalphaDeltaN repressed IL-1beta-induced, but not PMA-induced, cycloxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) expression. These data conclusively demonstrate a substantial role for NF-kappaB in the co-ordinate induction of COX-2, mPGES and in the corresponding release of PGE2 by IL-1beta. However, other pathways are primarily responsible for PGE2 release induced by PMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Cell Line
  • Cyclooxygenase 2
  • Dinoprostone / metabolism*
  • Gene Expression Regulation, Enzymologic / genetics*
  • Genes, Reporter
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Humans
  • Interleukin-1 / pharmacology*
  • Intramolecular Oxidoreductases / genetics*
  • Isoenzymes / genetics*
  • Luminescent Proteins / genetics
  • Membrane Proteins
  • Microsomes / enzymology*
  • NF-kappa B / metabolism*
  • Prostaglandin-E Synthases
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured

Substances

  • Interleukin-1
  • Isoenzymes
  • Luminescent Proteins
  • Membrane Proteins
  • NF-kappa B
  • Green Fluorescent Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Dinoprostone
  • Tetradecanoylphorbol Acetate