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

活化蛋白 C 对 LPS 诱导的一氧化氮产生的影响

• 批准号: 14570247
• 负责人: YOKOCHI Takashi
• 金额: $ 2.62万
• 依托单位: AICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570247/
• 关键词: lipopolysaccharide; endotoxin; activated protein C; nitric oxide; macrophage; nuclear factor-kappaB; endotoxic shock; エンドトキシンショック; NO; NF-kappaB; p38; LPS; NO合成酵素

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.

用小鼠巨噬细胞RAW 264.7细胞检测了活化蛋白C对LPS诱导的一氧化氮（NO）产生的影响。LPS诱导的NO生成在活化蛋白C的存在下被显著抑制。活化的蛋白C也抑制干扰素-γ诱导的NO产生。这种抑制作用大致依赖于活化蛋白C的浓度。活化蛋白C抑制诱导型NO合成酶的表达。此外，活化的蛋白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仅下调核因子（NF）-κ B（B）的活化，而不影响丝裂原活化蛋白激酶（包括p38、Erk 1/2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。提示活化蛋白C可能对内毒素休克的治疗有一定的作用。

项目成果

Koide N.et al.: "Change of mouse CD5(+) B1 cells to a macrophage-like morphology induced by gamma interferon and inhibited by interleukin-4"Clin Diagn Lab Immunol. 19. 1169-1174 (2002)

Koide N.等人：“由γ干扰素诱导并受白细胞介素4抑制的小鼠CD5（）B1细胞向巨噬细胞样形态的变化”Clin Diagn LabImmunol。

Yoshida T, Koide N, Sugiyama T, Mon I, Yokochi T.: "A novel caspase dependent pathway is involved in apoptosis of human endothelial cells by Shiga toxins."Microbiol Immunol. 46. 697-700 (2002)

Yoshida T、Koide N、Sugiyama T、Mon I、Yokochi T.：“一种新的半胱天冬酶依赖性途径参与志贺毒素引起的人内皮细胞凋亡。”微生物免疫学。

Yoshida T, et al.: "Human microvascular endothelial cells resist Shiga toxins by IFN-gamma treatment in vitro"Microbiology. 49. 2609-2614 (2003)

Yoshida T 等人：“人体微血管内皮细胞通过体外 IFN-γ 处理抵抗志贺毒素”微生物学。

Zhao L, Ohtaki Y, Yamaguchi K, Matsushita M, Fujita T, Yokochi T, Takada H, Endo Y.: "LPS-induced platelet response and rapid shock in mice : contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system"Blood. 100

赵 L、Ohtaki Y、Yamaguchi K、Matsushita M、Fujita T、Yokochi T、Takada H、Endo Y.：“LPS 诱导的小鼠血小板反应和快速休克：LPS O 抗原区域的贡献和凝集素的参与

Koide N, Sugiyama T, Mon I, Mu MM, Hamano T, Yoshida T, Yokochi T.: "Change of mouse CD5(+) B1 cells to a macrophage-like morphology induced by gamma interferon and inhibited by interleukin-4."Clin Diagn Lab Immunol. 9. 1169-74 (2002)

Koide N、Sugiyama T、Mon I、Mu MM、Hamano T、Yoshida T、Yokochi T.：“小鼠 CD5( ) B1 细胞在 γ 干扰素诱导下转变为巨噬细胞样形态，并受白细胞介素 4 抑制。”临床