Differential regulation of prostaglandin E biosynthesis by interferon‐ γ in colonic epithelial cells

Cyclooxygenase (COX)‐2 expression and activity in response to pro‐inflammatory cytokines TNF α and IFN γ was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. TNF α induced concentration‐ and time‐dependent upregulation of COX‐2 mRNA, protein and prostaglandin (PG)E 2 synthesis. Co‐stimulation of TNF α with IFN γ resulted in reduced COX‐2 mRNA and protein expression. IFN γ had no effect on the stability of TNF α ‐induced COX‐2 mRNA. TNF α ‐induced PGE 2 biosynthesis was significantly enhanced by the simultaneous addition of IFN γ and was COX‐2 dependent. The combination of IFN γ and TNF α induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE 2 synthesis. These results suggest that, in terms of PGE 2 biosynthesis, IFN γ plays a negative regulatory role at the level of COX‐2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFN γ in inflammatory diseases.British Journal of Pharmacology (2004) 141 , 1091–1097. doi: 10.1038/sj.bjp.0705719