MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis
MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis
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DOI：
10.1016/j.bbrc.2010.08.012
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发表时间：
2010-09-03
影响因子：
3.1
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
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作者：
Ojiro, Keisuke;Ebinuma, Hirotoshi;Hibi, Toshifumi
我们探索了MyD88信号通路通过toll样受体（TLRs）介导病原体相关分子模式（PAMPs）的识别，在给药ConA诱导的自身免疫性肝炎小鼠模型中的病理作用。我们首先发现Con a处理和未处理的野生型（WT）小鼠（包括肝巨噬细胞）肝脏中表达了各种TLRs和MyD88分子。流式细胞术分析显示肝脏CD11b(+)CD11c（-）和CD11b(+)CD11c（+）抗原呈递细胞表达TLR2，而NK和NKT细胞不表达TLR2。当WT和MyD88（-/-）小鼠静脉注射Con A时，在组织病理学、血清转氨酶和促炎细胞因子（tnf - α、ifn - γ和IL-6）水平以及肝巨噬细胞上/内CD80/CD86和tnf - α的上调方面，Con A注射MyD88（-/-）小鼠的肝炎严重程度明显低于WT小鼠。这些结果为TLRs-MyD88信号通路在自身免疫性肝炎模型中激活表达tlr的肝巨噬细胞提供了可能的证据，从而表明通过肠腔阻断病理病原体的策略可能是可行的。(C) 2010爱思唯尔公司版权所有。
We have explored the pathological role of the MyD88 signaling pathway via Toll-like receptors (TLRs) that mediate the recognition of pathogen-associated molecular patterns (PAMPs) in a murine model of autoimmune hepatitis induced by administering Concanavalin A (ConA). We first found that various TLRs and MyD88 molecules were expressed in liver of Con A-treated and untreated wild-type (WT) mice including liver macrophages. Flowcytometric analysis revealed that liver CD11b(+)CD11c(-) and CD11b(+)CD11c(+) antigen-presenting cells express TLR2, although NK and NKT cells did not. When WT and MyD88(-/-) mice were intravenously administered with Con A, the severity of hepatitis was significantly lower in Con A-injected MyD88(-/-) mice than in WT mice in terms of the histopathology, the levels of serum transaminase and pro-inflammatory cytokines (TNF-alpha, IFN-gamma, and IL-6), and upregulation of CD80/CD86 and TNF-alpha on/in liver macrophages. The results provide evidence of a possible contribution of the TLRs-MyD88 signaling pathway in activating TLR-expressing liver macrophages in the autoimmune hepatitis model, and thus indicate that the strategy of blockade of pathological pathogens via the intestinal lumen may be feasible for the treatment of the disease. (C) 2010 Elsevier Inc. All rights reserved.