Hypoxia upregulates cyclooxygenase-2 and prostaglandin E₂ levels in human peritoneal fibroblasts

Objective: To determine the levels of COX-1, COX-2, and prostaglandin (PG) E₂ in human fibroblasts isolated from normal peritoneal and adhesion tissues. Design: Prospective experimental study. Setting: University medical center. Patient(s): Fibroblast cultures from both peritoneum and adhesion tissues of five patients. Intervention(s): Treatment of the primary cultured fibroblasts with NS398. Main Outcome Measure(s): We used Western blot to determine the effects of hypoxia on COX-1 and COX-2 levels from lysates of normal peritoneal and adhesion fibroblasts before and after hypoxia. We also used the ELISA techniques to determine PGE₂ levels in media collected from these fibroblasts before and after hypoxia and with and without NS398, a COX-2-specific inhibitor. Result(s): There was no difference in COX-1 levels between normal and adhesion fibroblasts with and without hypoxia. Basal COX-2 and PGE₂ levels were significantly higher in adhesion than normal fibroblasts. Hypoxia gradually increased COX-2 and PGE₂ levels in normal peritoneal fibroblasts over time, reaching a peak at 24 hours but had no effect on adhesion fibroblasts. Inhibition of COX-2 by NS398 significantly reduced PGE₂ levels in both normal and adhesion fibroblasts. Conclusion(s): The presence of higher levels of COX-2 in adhesion fibroblasts and the induction of COX-2 in normal peritoneal fibroblasts in response to hypoxia indicate a possible inflammatory response. Regulation of COX-2 may alter peritoneal healing and may provide the opportunity to reduce postoperative adhesion development.