Petit J F, Schott C, Lepoivre M, Stoclet J C
Laboratoire de Biochimie- Biophysique, CNRS URA 1116, Université de Paris 11, Orsay, France.
Biochem Biophys Res Commun. 1990 Nov 30;173(1):1-5. doi: 10.1016/s0006-291x(05)81012-5.
Treatment of EMT 6 mammary adenocarcinoma cells with Interferon-gamma (IFN-gamma, 10 U.ml-1) plus endotoxin lipopolysaccharide (LPS, 100 ng.ml-1) induces concomitantly a growth arrest and production of citrulline and nitrite from L-arginine. A similar L-arginine-dependent metabolism is responsible for the vascular smooth muscle relaxing effect of stimulated endothelial cells. We therefore investigated the ability of EMT 6 cells to induce the relaxation of endothelium-denuded rat aortic rings precontracted with noradrenaline (1 microM). Pretreatment of EMT 6 cells with IFN-gamma + LPS increased their relaxing potency by 5-10 times. The relaxin effects of control and treated EMT 6 cells were entirely counteracted by NG-monomethyl-L-arginine (300 microM), a specific inhibitor of nitrite and citrulline production from L-arginine, and by methylene blue (10 microM) and LY 83583 (10 microM), two inhibitors of NOo-induced activation of guanylate cyclase. The effect of NG-monomethyl-L-arginine was reversed by L- but not D-arginine (1 mM). It is concluded that IFN-gamma + LPS increase the production of a relaxing factor in EMT 6 cells through the L-arginine-NOo-synthase pathway.
用γ干扰素（IFN-γ，10 U/ml）加内毒素脂多糖（LPS，100 ng/ml）处理EMT 6乳腺腺癌细胞，可同时诱导细胞生长停滞，并使L-精氨酸生成瓜氨酸和亚硝酸盐。类似的L-精氨酸依赖性代谢负责刺激内皮细胞后产生的血管平滑肌舒张作用。因此，我们研究了EMT 6细胞诱导去内皮的、用去甲肾上腺素（1 μM）预收缩的大鼠主动脉环舒张的能力。用IFN-γ + LPS预处理EMT 6细胞可使其舒张能力提高5至10倍。对照和处理后的EMT 6细胞的舒张作用完全被NG-单甲基-L-精氨酸（300 μM，L-精氨酸生成亚硝酸盐和瓜氨酸的特异性抑制剂）、亚甲蓝（10 μM）和LY 83583（10 μM，两种一氧化氮（NO）诱导的鸟苷酸环化酶激活抑制剂）所抵消。NG-单甲基-L-精氨酸的作用可被L-精氨酸（1 mM）而非D-精氨酸逆转。得出的结论是，IFN-γ + LPS通过L-精氨酸-NO合酶途径增加EMT 6细胞中舒张因子的产生。
