Role of intracellular redox in crosstalk between TH1/TH2 balance and nature immunity

细胞内氧化还原在 TH1/TH2 平衡与自然免疫之间的串扰中的作用

• 批准号: 14570403
• 负责人: DOBASHI Kunio
• 金额: $ 2.3万
• 依托单位: Gunma 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-14570403/
• 关键词: TH1; TH2 balance; glutathione; IL-12; oxidative stress; Toll-like receptor; GSH; GSSG; MAP kinase; レドックス; Th1・Th2バランス; MAPキナーゼ

We recently demonstrated that balance of reduced and oxidized glutathione level (GSH/GSSG) in macrophage (MΦ) play a central role in determining which of the TH1 and TH2 cytokine responses predominate during immune states through IL-12 production. In this study, we investigated whether changes in intra-cellular GSH/GSSG balance regulate LPS-induced IL-12 production and defined the molecular mechanism that underlies glutathione redox regulation.Glutathione redox regulates LPS-induced IL-12 production through p38 MAP kinase activation. (Ref 5) On the other hand, c-jun N-terminal kinase negatively regulates LPS-induced IL-12 production from MΦ, and glutathione redox regulates LPS-induced IL-12 production through the opposite control of JNK and p38 MAP kinase activation. (Ref 1)And, we revealed that TH1 and TH2 cytokines up and down-regulated the expression of Toll-like receptor 4 respectively, and that the crosstalk between TH1・TH2 balance and innate immunity. (Ref 3)Furthermore, TGF-β 1-induced CTGF mRNA expression in human lung fibroblasts is mediated through the JNK-dependent pathway. (Ref 2)

我们最近发现，在免疫状态下，巨噬细胞（MΦ）中还原型和氧化型谷胱甘肽水平（GSH/GSSG）的平衡通过IL-12的产生在决定TH 1和TH 2细胞因子应答中的哪一种占主导地位方面起着核心作用。在本研究中，我们研究了细胞内GSH/GSSG平衡的变化是否调节LPS诱导的IL-12产生，并确定了谷胱甘肽氧化还原调节的分子机制。(Ref 5）另一方面，c-jun N-末端激酶负性调节LPS诱导的MΦ产生IL-12，谷胱甘肽氧化还原通过JNK和p38 MAP激酶激活的相反控制来调节LPS诱导的M Φ产生IL-12。(Ref（1）揭示了TH 1和TH 2细胞因子分别上调和下调Toll样受体4的表达，并揭示了TH 1·TH 2平衡与天然免疫之间的相互作用。(Ref 3）TGF-β 1诱导的人肺成纤维细胞CTGF mRNA表达是通过JNK介导的。(Ref（二）

项目成果

Utsugi M: "c-Jun N-terminal kinase negatively regulates lipopolysaccharide-induced IL-12 production in human macrophages :"J Immunol.. 171. 628-635 (2003)

Utsugi M：“c-Jun N 末端激酶负调节人巨噬细胞中脂多糖诱导的 IL-12 产生：”J 免疫学杂志 171. 628-635 (2003)

Utsugi M, Dobashi K, Ishizuka T, Endou K, Hamuro J, Murata Y, Nakazawa T, Mori M.: "c-Jun N-terminal kinase negatively regulates lipopolysaccharide-induced IL-12 production in human macrophages : role of mitogen-activated protein kinase in glutathione red

Utsugi M、Dobashi K、Ishizuka T、Endou K、Hamuro J、Murata Y、Nakazawa T、Mori M.：“c-Jun N 末端激酶负调节人巨噬细胞中脂多糖诱导的 IL-12 产生：丝裂原的作用-

Utsugi M., Dobashi, K.et al.: "C-Jun-NH2-terminal kinases mediates expression of connective tissue growth factor induced by transforming growth factor-betal in human lung fibroblasts"Am. J. Respir. Cell Mol. Biol.. (In press). (2003)

Utsugi M.，Dobashi，K.等：“C-Jun-NH2-末端激酶介导人肺成纤维细胞中转化生长因子-β诱导的结缔组织生长因子的表达”Am。

Utsugi M: "Ambroxol inhibits platelet-derived growth factor production in human monocytic cells."Eur J Pharmacol. 436. 47-51 (2002)

Utsugi M：“氨溴索抑制人单核细胞中血小板衍生生长因子的产生。”Eur J Pharmacol。

Ishizuka T: "Interleukin-5 messenger RNA expression in peripheral blood mononuclear cells from patients with bronchial asthma and eosinophilia."Allergy Asthma Proc.. 23. 175-179 (2002)

Ishizuka T：“支气管哮喘和嗜酸性粒细胞增多症患者外周血单核细胞中白细胞介素 5 信使 RNA 的表达。”Allergy Asthma Proc.. 23. 175-179 (2002)