196: Cyclooxygenase-2 Inhibitors Enhances Apoptosis Of Adhesion Fibroblasts

Abstract

Cycloogenase-2 (COX-2), one of the rate limiting enzymes of prostaglandin (PG) synthesis, may play a role in regulating the development of postsurgical adhesions. We have previously reported the COX-2 and PGE2 levels are significantly higher in adhesions as compared to normal fibroblasts. We have also previously shown that normal peritoneal fibroblasts have a higher apoptosis rate as compared to adhesion fibroblasts. We have also found that hypoxia increases COX-2 and PGE2 levels in normal peritoneal fibroblasts and decrease their rate of apoptosis, which may contribute to the formation of postoperative adhesions. The objective of this project is to determine the effects of COX-2 inhibition on the rate of apoptosis of fibroblasts primary cultures established from normal peritoneum and adhesion tissues of the same patient. Fibroblasts from normal peritoneal and adhesion tissues were cultured under normal condition for 24 hours and treated with 100 microM NS398, a COX-2 inhibitor, for 4 hrs before evaluating apoptosis by the TUNEL assay and flow cytometry. University research laboratory. Women with adhesions undergoing gynecologic surgery. NS398 a COX-2 inhibitor. Baseline apoptosis was less in adhesion fibroblasts (2% apoptotic cells) as compared to normal peritoneal fibroblasts (30% apoptotic cells). NS398 treatment resulted in an increase in the rate of apoptosis in adhesion fibroblasts (27% apoptotic cells) but with not effects on normal fibroblasts (31% apoptotic cells). Our data suggests that adhesion fibroblasts may respond to the inhibition of COX-2 by increasing their rate of apoptosis. Inhibition of COX-2 may be important for the elimination of the adhesion fibroblasts during peritoneal healing.