Human retinal pigmented epithelial cells produce nitric oxide in response to cytokines

The present study demonstrates that human retinal pigmented epithelial cells produce nitric oxide (NO) upon co-treatment with interferon gamma (IFN gamma) and interleukin-1 beta (IL-1 beta). The biosynthesis of NO, which was measured by the accumulation of the stable end-product nitrite, requires an induction period of approximately 12 hours and continues for at least three days. The synthesis was abolished by the stereoselective inhibitors of NO synthase (NOS), NG-monomethyl-L-arginine, N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester and by cycloheximide. Transforming growth factor beta suppressed cytokine-induced NOS. The results indicate that cytokines such as IFN gamma and IL-1 beta are capable of inducing NOS, while TGF beta prevents this induction, in subcultured pigmented epithelial cells from the human retina.