Park Y C, Lee C H, Kang H S, Chung H T, Kim H D
Department of Molecular Biology, Pusan National University, Korea.
Biochem Biophys Res Commun. 1997 Nov 26;240(3):692-6. doi: 10.1006/bbrc.1997.7722.
To elucidate the role of phosphatidylinositol-3-kinase (PI3K) during macrophage activation, we examined the effects of wortmannin, a specific inhibitor of PI3K, on the induction of nitric oxide (NO) synthesis and tumor necrosis factor-alpha (TNF-alpha) secretion from lipopolysaccharide (LPS)-stimulated macrophages. Wortmannin had no effects on NO synthesis and TNF-alpha secretion by itself. Wortmannin markedly potentiated the LPS-induced NO production in a dose-dependent manner. Western blot analysis demonstrated that significantly increased levels of iNOS protein were expressed in LPS-stimulated macrophages treated with wortmannin, compared to those without LPS. Furthermore, enhancement of TNF-alpha secretion was observed in the initiation stage for activation of LPS-stimulated macrophages treated with wortmannin. These results suggest that PI3K plays an important role in transducing the signal that is involved in LPS-induced macrophage activation.
为阐明磷脂酰肌醇-3激酶（PI3K）在巨噬细胞激活过程中的作用，我们研究了PI3K的特异性抑制剂渥曼青霉素对脂多糖（LPS）刺激的巨噬细胞中一氧化氮（NO）合成诱导及肿瘤坏死因子-α（TNF-α）分泌的影响。渥曼青霉素自身对NO合成和TNF-α分泌无影响。渥曼青霉素以剂量依赖方式显著增强LPS诱导的NO生成。蛋白质印迹分析表明，与未用LPS处理的巨噬细胞相比，用渥曼青霉素处理的LPS刺激的巨噬细胞中诱导型一氧化氮合酶（iNOS）蛋白水平显著升高。此外，在用渥曼青霉素处理的LPS刺激的巨噬细胞激活起始阶段观察到TNF-α分泌增强。这些结果表明，PI3K在转导参与LPS诱导的巨噬细胞激活的信号中起重要作用。
