Production of Cytokines After Stimulation of Bacterial Components And Protective Role of the Cytokines to Bacterial Infection

细菌成分刺激后细胞因子的产生及其对细菌感染的保护作用

• 批准号: 01480180
• 负责人: NAKANO Masayasu
• 金额: $ 3.46万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480180/
• 关键词: Lipopolysaccharide (LPS); Cytokine; Protection against infection; Salmonella; Pseudomonas aeruginosa; 内毒素; 菌体成分

1. Mechanisms of macrophage activation by bacterial lipopolysaccharide (LPS). When murine peritoneal macrophages are stimulated by LPS, the macrophages produce various kinds of cytokines, and augment their bactericidal capacity. We investigated biochemical events in the macrophages after the stimulation of LPS. Calmodulin system was relevant to the macrophage activation by LPS to produce IL-1, while protein-kinase C and cyclic AMP as well as cyclic GMP seemed to be irrelevant to it. Shortly after LPS-stimulation, some proteins in the cell membrane and cytosol of the macrophages were phosphorylated. We purified the most dominant phosphorylated protein (pp65) in the cytosol, and found that the pp 65 was a substrate of serine kinase with a structure similar to human plastin.2. Protective role of cytokines in the bacterial infection. When some of recombinant cytokines (either IFN-gamma, TNF-alpha and beta, IL-1, IL-6, or G-CSF) was injected into mice, bactericidal capacity and protectivity in the mice against Salmonella typhimurium (or S. enteritidis) and Pseudomonas aeruginosa were augmented. Combination of some of the cytokines or cytokine plus LPS was more effective. The augmentaion was partly due to the recruitment of phagocytic cells and the increment of the phagocytic and killing abilities of individual cells.

1.细菌脂多糖（LPS）激活巨噬细胞的机制。当小鼠腹腔巨噬细胞被LPS刺激时，巨噬细胞产生各种细胞因子，并增强其杀菌能力。我们研究了LPS刺激后巨噬细胞中的生化事件。钙调素系统与LPS激活巨噬细胞产生IL-1有关，而蛋白激酶C、cAMP和cGMP与此无关。我们纯化了胞浆中最主要的磷酸化蛋白pp 65，发现pp 65是丝氨酸激酶的底物，其结构类似于人的质体蛋白.细胞因子在细菌感染中的保护作用。当将某些重组细胞因子（IFN-γ、TNF-α和TNF-β、IL-1、IL-6或G-CSF）注射到小鼠体内时，小鼠对鼠伤寒沙门氏菌（或S.铜绿假单胞菌（Pseudomonasaeruginosa）和铜绿假单胞菌（Pseudomonasaeruginosa）增加。某些细胞因子联合或细胞因子与LPS联合应用效果更好。这种增强部分是由于吞噬细胞的募集和单个细胞吞噬、杀伤能力的增强。

项目成果

M.Nakano: "Toxicity of Microcytis aeruginosa K-139 strain" Microbiology and Immnology. 33. 789-792 (1989)

M.Nakano：“铜绿微囊藻 K-139 菌株的毒性”微生物学和免疫学。

Nakano,M.,Terada,Y.,Matsumura,H.,and Shinomiya,H.: "Possible refractory site on LPSーinduced interleukin 1 production in C3H/HeJ peritoneal macrophages" Advances in experimental medicine and biology. 256. 347-359 (1990)

Nakano, M.、Terada, Y.、Matsumura, H. 和 Shinomiya, H.：“C3H/HeJ 腹膜巨噬细胞中 LPS 诱导的白细胞介素 1 产生的可能难治位点”实验医学和生物学进展 256。 347-。 359 (1990)

Nakano,M.,and Shinomiya,H.: "Cellular and Molecular Aspects of Endotoxin Reaction (pp.205ー214,Molecular mechanisms of macrophage actevation by LPS)" Editors:Nowotny,A.,et al.Publisher:Elsevier,Amsterdem, (566)

Nakano, M. 和 Shinomiya, H.：“内毒素反应的细胞和分子方面（第 205-214 页，LPS 巨噬细胞激活的分子机制）” 编辑：Nowotny, A. 等人 出版商：Elsevier，阿姆斯特丹, (566)

Friedman,H.,Klein,T.W.,Nakano,M.,and Nowotny,A.: "Endotoxin" Plenum Press,New York, 715 (1990)

Friedman,H.、Klein,T.W.、Nakano,M. 和 Nowotny,A.：“内毒素”全会出版社，纽约，715 (1990)

H.Matsumura: "Effect of murine recombinant interferon-γ in the protection of mice against Salmonella" International Journal of Immunopharmacology. 12. 49-65 (1990)

H.Matsumura：“鼠重组干扰素-γ 在保护小鼠免受沙门氏菌侵害方面的作用”《国际免疫药理学杂志》12. 49-65 (1990)。