Transforming growth factor-beta2 inhibition of corneal endothelial proliferation mediated by prostaglandin.
OBJECTIVE
To determine the influence of Prostaglandin (PG) E2 on transforming growth factor (TGF)-beta2-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-beta2 and/or indomethacin. To evaluate the inhibitory effects of PGE2 and TGF-beta2 on CE proliferation, the number of cells grown with exogenous PGE2, or TGF-beta2 with or without indomethacin pretreatment was determined.


RESULTS
TGF-beta2, 0.5 to 50 ng/ml, increased the PGE2 secretion of CE dose-dependently in a time-dependent manner. Indomethacin (> or =0.1 microg/ml) inhibited this PGE2 secretion to a low level (around 5-10 ng/ml) in the presence or absence of exogenous TGF-beta2. Both exogenous TGF-beta2 and PGE2 inhibited CE proliferation dose-dependently over a wide range of concentrations. Indomethacin reversed the inhibitory effects of TGF-beta2 but not those of exogenous PGE2. In the medium supplemented with indomethacin, even in the presence of 50 ng/ml of TGF-beta2, CE growth did not differ from control cultures.


CONCLUSIONS
TGF-beta2 stimulates PGE2 synthesis in CE and inhibits CE proliferation in a dose-dependent manner. Indomethacin extinguishes the inhibitory effects of TGF-beta2 on CE proliferation but not the effect of exogenous PGE2. These data suggest that the antiproliferative effects of TGF-beta2 on CE may be possibly due to TGF-beta2-induced synthesis of PG, most likely PGE2.


CONCLUSIONS
Inhibition of endogenous prostaglandins synthesis by indomethacin extinguished the inhibitory effects of Transforming Growth Factor-beta2 on corneal endothelium proliferation but not exogenous prostaglandin E2. It suggesting that TGF-beta2-induced autocrine synthesis of PGs, most likely PGE2, may be responsible for the anti-proliferative effects of TGF-beta2 on corneal endothelium.
Chen
Ko-Hua
KH
Department of Ophthalmology, Taipei Veterans General Hospital, #201 Shih-Pai Road, Section II, Taipei, 11217 Taiwan. khchen@vghtpe.gov.tw
Hsu
Wen-Ming
WM
Chiang
Chien-Cheng
CC
Li
Yen-Shien
YS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004728:Endothelium, Corneal / Q000166:cytology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011817:Rabbits; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003470:Culture Media; D004338:Drug Combinations; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D015232:Dinoprostone; D007213:Indomethacin