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

Abstract

Prostaglandin (PG) E 2 release is induced in pulmonary A549 cells by the NF-κB-activating stimuli interleukin-1β (IL-1β) and phorbol 12-myristate 13-acetate (PMA). Adenoviral over-expression of IκBαΔN, a dominant NF-κB inhibitor, prevents NF-κB-dependent transcription and was used to qualify the role of NF-κB in the release of PGE 2 . IκBαΔN repressed IL-1β-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-κB in the co-ordinate induction of COX-2, mPGES and in the corresponding release of PGE 2 by IL-1β. However, other pathways are primarily responsible for PGE 2 release induced by PMA.