Nonsteroidal anti-inflammatory drugs may delay the repair of gastric mucosa by suppressing prostaglandin-mediated increase of hepatocyte growth factor production

Prostaglandins (PGs), hepatocyte growth factor (HGF), and induction of cyclooxygenase (PG synthetase, COX) play important roles in the repair process of gastric mucosa. We hypothesized that nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin (IND), retard the healing of ulcers by suppressing these factors, In this study, we investigated the effects of cytokines, growth factors, and IND on production of PG and HGF, and induction of COX using cultured human gastric fibroblasts. Exogenous PGs significantly increased HGF production in a dose-dependent manner. Among various potential stimulants tested, interleukin-1 beta (IL-1 beta) dramatically increased PGE(2) production and significantly stimulated HGF production. IL-1 beta induced COX-2 but not COX-1 protein. IND significantly reduced both basal and IL-1 beta-induced PGE(2) release and HGF production. These results suggest that the IL-1 beta-PG-HGF pathway plays a role in the repair process of gastric mucosa. Further, NSAIDs may delay the healing of gastric mucosal ulcer, in part through suppression of HGF expression via inhibition of endogenous PG production. (C) 1998 Academic Press.