Interferon-gamma-mediated tissue factor expression contributes to T-cell-mediated fulminant hepatitis through induction of hyper coagulation in mice

干扰素-γ介导的组织因子表达通过诱导小鼠高凝血而导致 T 细胞介导的暴发性肝炎

• 批准号: 24659806
• 负责人: TSUTSUI Hiroko
• 金额: $ 2.33万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659806/
• 关键词: 劇症肝炎; Concanavalin A; 微小循環傷害; 組織因子; interferon gamma; Tumor necrosis factor; クッパー細胞; 肝類洞内皮細胞; Interferon gamma; Tumor Necrosis Factor; 血栓性肝炎; STAT1; Kupffer細胞; 類洞内皮細胞

Concanavalin A (Con A) treatment induces fulminant hepatitis in mice in a manner dependent on interferon (IFN)-gamma. As previously reported, treatment with the anticoagulant heparin protects against Con A hepatitis, despite healthy production of IFN-gamma. Here, we investigated the mechanisms for hypercoagulation-mediated hepatitis. Mice deficient in IFN-gamma were resistant to Con A hepatitis without induction of systemic and hepatic hypercoagulation. This suggests that IFN-gamma is necessary for the thrombus-associated changes. Neutralization of tissue factor, that is essential for the activation of coagulation cascade, resulted in the protection of this hepatitis despited normal induction of IFN-gamma. Responsiveness to IFN-gamma was required for both hepatic macrophages and endothelial cells, which expressed tissue factor after Con A challenge. Thus, proinflammatory signal elicited by IFN-gamma in various liver cells is necessary for the development of Con A hepatitis.

伴刀豆球蛋白A（Con A）治疗以依赖于干扰素（IFN）-γ的方式诱导小鼠暴发性肝炎。如前所述，尽管IFN-γ的产生是健康的，但用抗凝肝素治疗可以预防Con A肝炎。在这里，我们调查了高凝介导的肝炎的机制。IFN-γ缺乏的小鼠对Con A肝炎具有抗性，而不会诱导全身和肝脏高凝状态。这表明IFN-γ是血栓相关变化所必需的。尽管IFN-γ的正常诱导，组织因子的中和（对于凝血级联的激活至关重要）仍对这种肝炎产生了保护作用。肝巨噬细胞和内皮细胞对IFN-γ的反应性是必需的，它们在Con A激发后表达组织因子。因此，IFN-γ在各种肝细胞中引起的促炎信号对于Con A肝炎的发展是必要的。

项目成果

Hepatology誌に論文が掲載されました

论文发表于Hepatology杂志

兵庫医科大学

兵库医科大学

Contribution of IFN-γ/STAT1 signaling to T cell-mediated hepatitis through induction of hepatic hypercoagulation status. (Symposium)

IFN-γ/STAT1 信号传导通过诱导肝脏高凝状态对 T 细胞介导的肝炎的贡献（研讨会）。

• 发表时间: 2012
• 作者: 岡本共弘;内山良介;西口修平;筒井ひろ子;Tsutsui H.
• 通讯作者: Tsutsui H.

Concanavalin A重症肝炎の責任病態である肝局所DICにおける,IFNγ/STAT1に依存した組織因子発現誘導の重要性

IFNγ/STAT1 依赖性组织因子表达诱导在肝脏局限性 DIC 中的重要性，这是导致伴刀豆球蛋白 A 型严重肝炎的病理状况

• 发表时间: 2012
• 作者: 岡本共弘;内山良介;西口修平;筒井ひろ子
• 通讯作者: 筒井ひろ子

Interferon-gamma-mediated tissue factor expression contributes to T-cell-mediated hepatitis through induction of hypercoagulation in mice

• DOI: 10.1002/hep.26027
• 发表时间: 2013-01-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Kato, Junko;Okamoto, Tomohiro;Tsutsui, Hiroko
• 通讯作者: Tsutsui, Hiroko