Hori T, Kashiyama S, Hayakawa M, Shibamoto S, Tsujimoto M, Oku N, Ito F
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Exp Cell Res. 1989 Nov;185(1):41-9. doi: 10.1016/0014-4827(89)90035-9.
Recombinant human tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in serum-free culture medium. However, TNF had a cytotoxic effect upon the growth of FS-4 cells in combination with arachidonic acid. When arachidonic acid was added to culture medium in the absence of TNF, however, it had no effect on the cell growth. Arachidonic acid inhibited the TNF-induced cell growth in a dose-dependent manner: it reversed the TNF-stimulated growth to the control level at a concentration of 10 microM and was cytotoxic to TNF-treated FS-4 cells at higher concentrations. This cytotoxicity of TNF was not observed in FS-4 cells treated with palmitic acid. Indomethacin, a cyclooxygenase inhibitor, decreased the cytotoxic effect that TNF exerted in the presence of arachidonic acid. These results suggest that TNF becomes cytotoxic to FS-4 cells when arachidonic acid present in the culture medium is converted to prostaglandins.
重组人肿瘤坏死因子(TNF)在无血清培养基中刺激汇合的人成纤维细胞(FS-4)生长。然而,TNF与花生四烯酸联合时对FS-4细胞的生长具有细胞毒性作用。然而,当在无TNF的情况下将花生四烯酸添加到培养基中时,它对细胞生长没有影响。花生四烯酸以剂量依赖的方式抑制TNF诱导的细胞生长:在10 microM的浓度下,它将TNF刺激的生长逆转至对照水平,并且在更高浓度下对TNF处理的FS-4细胞具有细胞毒性。在用棕榈酸处理的FS-4细胞中未观察到TNF的这种细胞毒性。环氧化酶抑制剂吲哚美辛降低了TNF在花生四烯酸存在下所发挥的细胞毒性作用。这些结果表明,当培养基中存在的花生四烯酸转化为前列腺素时,TNF对FS-4细胞具有细胞毒性。