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

用正常人胃和结肠成纤维细胞研究了非甾体抗炎药吲哚美辛（NSAID）对肝细胞生长因子（HGF）表达的影响。结果如下：a.人胃和结肠成纤维细胞产生HGF.B.前列腺素（PGs）刺激HGF的产生。效力的顺序为PGE 1 * PGE 2> PGI 2类似物。c.外源性cAMP和霍乱毒素增加HGF产生。d. PGE 1增加细胞cAMP。e.在FGF、TGF α、EGF、TNF-α和IL 1-β中，只有IL 1-β显著增加内源性PGE 2的产生。f. IL 1-β诱导的不是环加氧酶（考克斯）-1而是考克斯-2。g.吲哚美辛完全阻断IL 1-β诱导的PGE 2的增加。h. IL 1-β增加HGF，这些结果表明，NSAID可能通过抑制内源性PG的产生来抑制PG诱导的HGF产生的增加。这可能部分解释了胃损伤和抑制结肠癌发生的NSAIDs的机制。

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.