Hypoxia upregulates cyclooxygenase-2 and prostaglandin E(2) levels in human peritoneal fibroblasts.

OBJECTIVE

To determine the levels of COX-1, COX-2, and prostaglandin (PG) E(2) in human fibroblasts isolated from normal peritoneal and adhesion tissues.

METHODS

Prospective experimental study.

METHODS

University medical center.

METHODS

Fibroblast cultures from both peritoneum and adhesion tissues of five patients.

METHODS

Treatment of the primary cultured fibroblasts with NS398.

METHODS

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 PGE(2) levels in media collected from these fibroblasts before and after hypoxia and with and without NS398, a COX-2-specific inhibitor.

RESULTS

There was no difference in COX-1 levels between normal and adhesion fibroblasts with and without hypoxia. Basal COX-2 and PGE(2) levels were significantly higher in adhesion than normal fibroblasts. Hypoxia gradually increased COX-2 and PGE(2) 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 PGE(2) levels in both normal and adhesion fibroblasts.

CONCLUSIONS

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.