IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase.
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.
Catley
Matthew C
MC
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College Faculty of Medicine, SW3 6LY, London, UK.
Chivers
Joanna E
JE
Cambridge
Lisa M
LM
Holden
Neil
N
Slater
Donna M
DM
Staples
Karl J
KJ
Bergmann
Martin W
MW
Loser
Peter
P
Barnes
Peter J
PJ
Newton
Robert
R
D000256:Adenoviridae / Q000235:genetics; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D007527:Isoenzymes; D008164:Luminescent Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D049452:Green Fluorescent Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate