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

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.