Abstract
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 PGE2 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 PGE2 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alprostadil / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cholera Toxin / pharmacology
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / metabolism
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Cyclooxygenase 1
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Cyclooxygenase 2
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Dinoprostone / pharmacology
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Fibroblasts
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Gastric Mucosa / drug effects*
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Gene Expression Regulation, Enzymologic / genetics
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Hepatocyte Growth Factor / pharmacology*
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Humans
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Indomethacin / pharmacology
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Interleukin-1 / pharmacology
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Isoenzymes / metabolism
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Membrane Proteins
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Peptic Ulcer
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Prostaglandin Antagonists / pharmacology
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Prostaglandin-Endoperoxide Synthases / metabolism
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Prostaglandins / pharmacology*
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Stomach Ulcer / metabolism
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Transforming Growth Factor alpha / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-1
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Isoenzymes
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Membrane Proteins
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Prostaglandin Antagonists
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Prostaglandins
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Transforming Growth Factor alpha
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Tumor Necrosis Factor-alpha
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Hepatocyte Growth Factor
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Cholera Toxin
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Cyclic AMP
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Alprostadil
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Dinoprostone
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Indomethacin