Effect of activated protein C on LPS-induced nitric oxide production

通过小鼠巨噬细胞RAW 264.7细胞，研究了活化蛋白C对lps诱导的一氧化氮（NO）生成的影响。活化蛋白C的存在显著抑制lps诱导的NO生成，活化蛋白C也抑制干扰素诱导的NO生成。这种抑制作用大致取决于活化蛋白C的浓度。活化蛋白C抑制了一种诱导型NO合成酶的表达。此外，活化蛋白C抑制lps诱导的肿瘤坏死因子(TNF)- α的产生以及NO的产生。活化蛋白C专一下调核因子κ B的活化，而不影响有丝分裂原活化蛋白激酶p38、Erkl/2和SAPK/JNK的活化。活化蛋白C对RAW 264.7细胞没有细胞毒性作用。因此，活化蛋白C可能对内源性休克治疗有用。

Effect of activated protein C on LPS-induced nitric oxide (NO) production was examined, by using mouse macrophage RAW 264.7 cells. LPS-induced NO production was significantly inhibited in the presence of activated protein C. Activated protein C also inhibited interferon-gamma-induced NO production. The inhibition was roughly dependent on the concentration of activated protein C. Activated protein C inhibited the expression of an inducible type of NO synthethase. Further, activated protein C suppressed LPS-induced tumor necrosis factor (TNF)-alpha production as well as, NO production. Activated protein C exclusively down-regulated the activation of nuclear factor (NF)-kappa B activation whereas it did not affect the activation of the mitogen-activated protein kinases including p38, Erkl/2 and SAPK/JNK. Activated protein C did not exhibit a cytotoxic action on RAW 264.7 cells. It was therefore suggested that activated protein C might be useful for endotoxic shock treatment.