TGF-BETA AND IL-1-BETA ACT IN SYNERGY TO ENHANCE IL-6 AND IL-8 MESSENGER-RNA LEVELS AND IL-6 PRODUCTION BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS

Cytokines produced by human retinal pigment epithelial (RPE) cells may function as important regulators of intraocular inflammation. We inve stigated the effect of transforming growth factor-beta (TGF-beta) on i nterleukin-beta (IL-beta) induction of IL-6 and IL-8 mRNA levels and p rotein production by human RPE cells. Both TGF-beta and IL-beta alone induce IL-6 mRNA and IL-6 production in human RPE cells and synergize to enhance IL-6 mRNA levels and IL-6 production over a range of TGF-be ta (0.1-10 ng/ml) and IL-beta concentrations (5-500 U/ml). TGF-beta wa s also found to enhance IL-1 beta induction of IL-8 mRNA levels at low er IL-1 beta concentrations (50 U/ml) but had no effect at higher IL-1 beta concentrations (50 U/ml). However, TGF-beta had no synergistic e ffect on IL-1 beta induction of IL-8 secretion. These results suggest that expression of IL-6 and IL-8 in human RPE cells is regulated by di fferent transcriptional and translational mechanisms, and that RPE cel ls are important regulators of cytokine production within the ocular m icroenvironment.