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 TNFα and IFNγ was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. TNFα induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E2 synthesis. Co-stimulation of TNFα with IFNγ resulted in reduced COX-2 mRNA and protein expression. IFNγ had no effect on the stability of TNFα-induced COX-2 mRNA. TNFα-induced PGE2 biosynthesis was significantly enhanced by the simultaneous addition of IFNγ and was COX-2 dependent. The combination of IFNγ and TNFα induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE2 synthesis. These results suggest that, in terms of PGE2 biosynthesis, IFNγ 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 IFNγ in inflammatory diseases. British Journal of Pharmacology (2004) 141, 1091–1097. doi:10.1038/sj.bjp.0705719