THE ROLE OF STRESS PROTEINS IN ENDOTOXIN-INDUCED HEPATIC INJURY

应激蛋白在内毒素引起的肝损伤中的作用

• 批准号: 09670303
• 负责人: YOKOCHI Takashi
• 金额: $ 1.98万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670303/
• 关键词: lipopolysaccharide; endotoxin; HSP; apoptosis; stress response; TNF; hepatocyte; endotoxic shock; TNFi; ストレス蛋白; マウス; エンドトキシンショック

The expression of heat shock proteins (HSPs) as stress-induced proteins was studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) as an experimental endotoxic shock model. The expression of constitutive type heat shock protein 70 (HSC70) was significantly reduced in livers of mice injected with D-GalN and LPS, while its expression was unaffected in livers of mice injected with D-GalN or LPS alone, The expression of other constitutive type HSPs, namely HSP 60, 32 and 25 was also reduced in mice injected with D-GalN and LPS.On the other hand, inducible type HSP70 was detected in livers from mice injected with D-GalN and LPS, but not in livers from mice injected with D-GalN or LPS alone.Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody prevented the liver from reduced expression of constitutive type HSC70, and lead to marked expression of inducible type HSP70 in the liver. Reduced expression of constitutive type HSC70 was also found when D-GalN and recombinant TNF-alpha was injected. Therefore, TNF-alpha was suggested to play an critical role on altered expression of constitutive HSC70 and inducible type HSP70 in response of D-GalN-sensitized mice to LPS.

以D-氨基半乳糖（D-GalN）和脂多糖（LPS）联合注射小鼠作为实验性内毒素休克模型，研究了应激诱导蛋白热休克蛋白（HSPs）的表达。在注射D-GalN和LPS的小鼠的肝脏中，组成型热休克蛋白70（HSC 70）的表达显著降低，而在单独注射D-GalN或LPS的小鼠的肝脏中，其表达不受影响。在注射D-GalN和LPS的小鼠中，其他组成型HSP，即HSP 60、32和25的表达也降低。在D-GalN和LPS联合注射的小鼠肝脏中检测到诱导型HSP 70，而在单独注射D-GalN或LPS的小鼠肝脏中未检测到诱导型HSP 70，同时注射抗肿瘤坏死因子（TNF）-α抗体可阻止肝脏中组成型HSP 70表达的减少，并导致诱导型HSP 70在肝脏中显著表达。当注射D-GalN和重组TNF-α时，也发现组成型HSC 70的表达减少。因此，提示TNF-α在D-GalN致敏小鼠对LPS的反应中对组成型HSC 70和诱导型HSP 70的表达改变起关键作用。

项目成果

G.Z.Jiang, Y.Kato, T.Sugiyama, N.Koide, D.Chakravortty, M.Kawai, M.Fukuda, T.Yoshida, T.Yokochi: "Role of CD86 (B7-2) in triggering of antigen-specific IgE antibody response by lipopolysaccharide" FEMS Immunol.Med.Microbiol. 21. 303-311 (1998)

G.Z.Jiang、Y.Kato、T.Sugiyama、N.Koide、D.Chakravortty、M.Kawai、M.Fukuda、T.Yoshida、T.Yokochi：“CD86 (B7-2) 在触发抗原特异性中的作用

T.Sugiyama, N.Kido, Y.Yutaka, N.Koide, T.Yoshida, T.Yokochi: "Generation of Escherichia coli O9a serotype, a subtype of E.coli O9, by transfer of the wb^* gene cluster of Klebsiella O3 into E.coli via recombination" J.Bacteriol. 180. 2775-2778 (1998)

T.Sugiyama、N.Kido、Y.Yutaka、N.Koide、T.Yoshida、T.Yokochi：“通过转移大肠杆菌 O9a 的 wb^* 基因簇，产生了大肠杆菌 O9a 血清型（大肠杆菌 O9 的一个亚型）

A.Morikawa,: "Role of nitric oxide in lipopolysaccharide-induced hepatic injury in D-galactosamine-sensitized mice as an experimental endotoxic shock model." Infect.Immun.in press.(1999)

A.Morikawa：“作为实验性内毒素休克模型，一氧化氮在 D-半乳糖胺致敏小鼠脂多糖诱导的肝损伤中的作用。”

N.Paeng,: "Experimental murine model for autoimmune enterocolitis using Klebsiella pneumoniae O3 lipopolysaccharide as a potent immnological adjuvant." Microbiol.Immunol.43. 45-52 (1999)

N.Paeng，：“使用肺炎克雷伯菌 O3 脂多糖作为有效的免疫佐剂的自身免疫性小肠结肠炎实验鼠模型。”

N.Kido, T.Sugiyama, T.Yokochi, H.Kobayashi, Y.Okawa: "Synthesis of Escherichia coli O9a polysaccharide requires the participation of two domains of WbdA,a mannosyltransferase encoded within the wb^* gene cluster" Mol.Microbiol. 27. 1213-1221 (1998)

N.Kido、T.Sugiyama、T.Yokochi、H.Kobayashi、Y.Okawa：“大肠杆菌 O9a 多糖的合成需要 WbdA 的两个结构域的参与，WbdA 是 wb^* 基因簇内编码的甘露糖基转移酶”Mol.Microbiol