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

Prostaglandin (PG) E-2 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 PGE(2). 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-kappabeta in the co-ordinate induction of COX-2, mPGES and in the corresponding release of PGE(2) by IL-1beta. However, other pathways are primarily responsible for PGE(2) release induced by PMA. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.