Endogenous interferon-γ induced by bacterial lipopolysaccbaride ; its production mechanism and roles as a mediator

细菌脂多糖诱导的内源性干扰素-γ的产生机制及其介导作用

基本信息

批准号：
13670280
负责人：
MATSUURA Motohiro
金额：
$ 2.18万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670280/
关键词：
Endotoxin Lipopolysaccharidc Interferon-γ Nitric oxide IL-12 IL-18

项目摘要

Host responses to bacterial lipopolysaccharide (LPS) are mediated by production of various mediators such as tumor necrosis factor (TNF), interleukin (IL)-6 and nitric oxide (NO). Interferon (IFN)-γ, which plays important roles in immune system, is detectable in vivo in the sera of LPS-injected animals but its induction mechanisms by LPS in vitro and its roles as an LPS mediator have not been well understood.Mouse peritoneal exudate cells (PEC) were cultured and stimulated with LPS for induction of mediators. In the presence of anti-IFN-γ, NO production in the PEC culture was remarkably suppressed but production of TNF and IL-6 was scarcely suppressed. Besides anti-IFN-γ, various antibodies against LPS mediators were examined and found that anti-IL-12 and anti-IL-18 showed suppressivc effect on LPS-induced production of NO and IFN-γ, and that these antibodies in synergy showed strong suppression. These cytokines, known as IFN-γ-inducing cytokines, stimulated in synergy the PEC for production of IFN-γ and NO. Macrophage population in the PEC prepared as adherent cells responded well to LPS for IL-12 production but weakly for production of IFN-γ and NO. The macrophages also responded well to IFN-γ for NO production. For production of IFN-γ by stimulation with LPS or IL12+IL18, non-adherent cells in the PEC culture were required. Considering these results all together, a pathway trough the production of intermediates such as IL-12 and IL-18 by macrophages that stimulate non-adherent cells for production of IFN-γ was revealed to play a main role in the LPS-induced IFN-γ production and the IFN-γ contributed largely to production of NO by macrophages but scarcely to production of TNF and IL-6.

宿主对细菌脂多糖（LPS）的反应是通过产生各种介质（例如肿瘤坏死因子（TNF），白介素（IL）-6和一氧化氮（NO）的各种介质的产生来介导的。干扰素（IFN）-γ在免疫系统中起重要作用，在体内在LPS注射动物的血清中被检测到，但LPS在体外的诱导机制及其作为LPS介质的作用尚未很好地理解。小鼠腹膜散发细胞（PEC）（PEC）被培养并通过LPS进行分类，以用于米甲米衍射。在存在抗IFN-γ的情况下，PEC培养物中没有产生很大的抑制，但是TNF和IL-6的产生几乎不会被抑制。除了抗IFN-γ外，还检查了针对LPS介质的各种抗体，发现抗IL-12和抗IL-18对LPS诱导的NO和IFN-γ的产生显示抑制IFN-IFN-γ的抑制作用，并且Synergy中的这些抗体表现出强抑制作用。这些细胞因子（称为IFN-γ诱导的细胞因子）在Synergy中刺激了PEC，用于生产IFN-γ和NO。 PEC中制备的巨噬细胞种群随着粘附细胞的响应良好，对IL-12产生的LP响应良好，但对于IFN-γ和NO的产生而言弱。巨噬细胞对IFN-γ的无生产也很好。为了通过用LPS或IL12+IL18刺激生产IFN-γ，需要PEC培养中的非粘附细胞。 Considering these results all together, a pathway trouble the production of intermediates such as IL-12 and IL-18 by macrophages that stimulate non-adherent cells for production of IFN-γ was revealed to play a main role in the LPS-induced IFN-γ production and the IFN-γ contributed largely to production of NO by macrophages but scarcely to production of TNF and IL-6.