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.