PIRFENIDONE REDUCES FIBRONECTIN SYNTHESIS BY CULTURED HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS

Purpose: Pirfenidone is a novel anti-fibrotic drug that has been shown to inhibit fibroblast growth and collagen synthesis induced by transf orming growth factor (TGF)-beta(1). In the present study we investigat ed the ability of pirfenidone to moderate fibronectin synthesis by cul tured human retinal pigment epithelial (RPE) cells main-rained in medi a containing 1% foetal bovine serum when stimulated with TGF-beta(1). Methods: Primary human RPE cultures were used.Treatments included TGF- beta(1), pirfenidone and pirfenidone with TGF-beta(1). After 72 h trea tments, cell growth was determined by cell counting and fibronectin wa s measured by ELISA. Results: Transforming growth factor-beta(1) (1-10 ng/mL) increased the production of soluble fibronectin, while pirfeni done (300 mu mol/L) significantly reduced the TGF-beta(1)-induced syn- thesis of fibronectin. Pirfenidone alone had no effect on fibronectin synthesis by cultured RPE cells. Conclusion: We conclude that the anti -fibrotic effect of pirfenidone may be partly mediated through inhibit ion of TGF-beta(1)-induced fibronectin synthesis.