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

采用正常人胃和结肠成纤维细胞，研究非甾体抗炎药吲哚美辛对肝细胞生长因子（HGF）表达的影响。结果如下：人胃和结肠成纤维细胞产生HGF。前列腺素（pg）刺激HGF的产生。效价顺序为PGE1 * PGE2 > PGI2类似物。c.外源性cAMP和霍乱毒素增加HGF的产生，d. pgel增加细胞cAMP。e.在FGF、TGFalpha、EGF、tnf - α和il - 1- β中，只有il - 1- β显著增加内源性PGE2的产生。il - 1- β诱导的COX-2 - g而非环氧化酶(COX)- 1。吲哚美辛完全阻断il - 1- β诱导的PGE2.h升高。il - 1- β使HGF升高，而吲哚美辛可阻止这一变化。这些结果表明，非甾体抗炎药可能通过抑制内源性PG生成来抑制PG诱导的HGF生成的增加。这可能部分解释了非甾体抗炎药胃损伤和抑制结肠癌发生的机制。

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.