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

1 Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNFalpha and IFNgamma was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. 2 TNFalpha induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E-2 synthesis. 3 Co-stimulation of TNFalpha with IFNgamma resulted in reduced COX-2 mRNA and protein expression. 4 IFNgamma had no effect on the stability of TNFalpha-induced COX-2 mRNA. 5 TNFalpha-induced PGE(2) biosynthesis was significantly enhanced by the simultaneous addition of IFNg and was COX-2 dependent. 6 The combination of IFNgamma and TNFalpha induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE(2) synthesis. 7 These results suggest that, in terms of PGE(2) biosynthesis, IFNgamma 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 IFNgamma in inflammatory diseases.