EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ON THE EXPRESSION OF GROWTH FACTORSAND THEIR RECEPTORS

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Effects of indomethacin, a NON-STEROIDAL ANTI-INFLAMMATORY DRUG (NSAID), on the expression of hepatocyte growth factor (HGF) were investigated using normal human gastric and colonic fibroblasts. Results are as follows ;a.Human gastric and colonic fibroblasts produced HGF.b.Prostaglandins (PGs) stimulated HGF production. The order of potency was PGE1 * PGE2 > PGI2 analogue.c.Exogenous cAMP and cholera toxin increased HGF production.d.PGEl increased cellular cAMP.e.Among FGF,TGFalpha, EGF,TNF-alpha, and IL1-beta, only IL1-beta dramatically increased endogenous PGE2 production.f.IL1-beta induced not cyclooxygenase (COX)-l but COX-2.g.Indomethacin completely blocked IL1-beta-induced increase of PGE2.h.IL1-beta increased HGF,which was prevented by indomethacin.These results suggest that NSAIDs may inhibit PG-induced increase of HGF production by suppressing endogenous PG production. This may explain in part the mechanisms of gastric injury and suppression of colon carcinogenesis by NSAIDs.