Transforming growth factor-ß2 inhibition of corneal endothelial proliferation mediated by prostaglandin

Purpose. To determine the influence of Prostaglandin (PG) E2 on transforming growth factor (TGF)-ß2-mediated inhibitory effects on the proliferation of corneal endothelial cells (CE). Methods. The PGE2 and cell proliferation assays were performed using cultured rabbit corneal endothelium. A PGE2-specific enzyme immunoassay was used to check PGE2 synthesis in supernatants of cells cultured with and without added TGF-ß2 and/or indomethacin. To evaluate the inhibitory effects of PGE2 and TGF-ß2 on CE proliferation, the number of cells grown with exogenous PGE2, or TGF-ß2 with or without indomethacin pretreatment was determined. Results. TGF-ß2, 0.5 to 50 ng/ml, increased the PGE2 secretion of CE dose-dependently in a time-dependent manner. Indomethacin (=0.1mg/ml) inhibited this PGE2 secretion to a low level (around 5-10 ng/ml) in the presence or absence of exogenous TGF-ß2. Both exogenous TGF-ß2 and PGE2 inhibited CE proliferation dose-dependently over a wide range of concentrations. Indomethacin reversed the inhibitory effects of TGF-ß2 but not those of exogenous PGE2. In the medium supplemented with indomethacin, even in the presence of 50 ng/ml of TGF-ß2, CE growth did not differ from control cultures. Conclusions. TGF-ß2 stimulates PGE2 synthesis in CE and inhibits CE proliferation in a dose-dependent manner. Indomethacin extinguishes the inhibitory effects of TGF-ß2 on CE proliferation but not the effect of exogenous PGE2. These data suggest that the antiproliferative effects of TGF-ß2 on CE may be possibly due to TGF-ß2-induced synthesis of PG, most likely PGE2.

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