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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来介导的，例如肿瘤坏死因子 (TNF)、白细胞介素 (IL)-6 和一氧化氮 (NO)。干扰素（IFN）-γ在免疫系统中发挥着重要作用，在体内可在注射LPS的动物血清中检测到，但其在体外的LPS诱导机制及其作为LPS介质的作用尚不清楚。培养并用LPS刺激小鼠腹膜渗出细胞（PEC）以诱导介质。在存在抗-IFN-γ的情况下，PEC培养物中NO的产生被显着抑制，但TNF和IL-6的产生几乎没有被抑制。除了抗IFN-γ之外，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的产生显示出抑制作用，并且这些抗体协同作用显示出强烈的抑制作用。这些细胞因子被称为 IFN-γ 诱导细胞因子，协同刺激 PEC 产生 IFN-γ 和 NO。 PEC 中的巨噬细胞群制备为贴壁细胞，对 LPS 产生 IL-12 反应良好，但对产生 IFN-γ 和 NO 反应较弱。巨噬细胞对 IFN-γ 也能产生良好的 NO 反应。为了通过 LPS 或 IL12+IL18 刺激产生 IFN-γ，需要 PEC 培养物中的非贴壁细胞。综合考虑这些结果，巨噬细胞产生 IL-12 和 IL-18 等中间体刺激非贴壁细胞产生 IFN-γ 的途径被揭示在 LPS 诱导的 IFN-γ 产生中起主要作用，并且 IFN-γ 很大程度上促进了巨噬细胞产生 NO，但几乎不促进 TNF 和 IL-6 的产生。