Cutting edge: Endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface Toll-like receptor 4 expression
Cutting edge: Endotoxin tolerance in mouse peritoneal macrophages correlates with down-regulation of surface Toll-like receptor 4 expression
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DOI：
10.4049/jimmunol.164.7.3476
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发表时间：
2000-04-01
影响因子：
4.4
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Nomura, F;Akashi, S;Akira, S
暴露于LPS的单核细胞/巨噬细胞对LPS第二次刺激的反应减弱，这被称为LPS耐受性。在本研究中，我们研究了巨噬细胞中LPS耐受性的分子机制。预暴露于LPS的小鼠腹腔巨噬细胞表现出炎症细胞因子的产生减少，且呈时间和剂量依赖性。在通过 LPS 预处理变得耐受的巨噬细胞中，未观察到 IL-1 受体相关激酶和 NF-κ B 的激活，表明 Toll 样受体 4 (TLR4)-MyD88 依赖性信号传导中的近端事件在耐受巨噬细胞中受到影响。尽管TLR4 mRNA表达在LPS预处理后数小时内显着下降，并在24 h恢复到原始水平，但表面TLR4表达在1 h内开始下降，此后逐渐下降，并在24 h内保持抑制状态，耐受巨噬细胞中炎症细胞因子产生的减少与表面TLR4表达的下调密切相关，这可能解释了LPS耐受的机制之一。
Monocytes/macrophages exposed to LPS show reduced responses to second stimulation with LPS, which is termed LPS tolerance, In this study, we investigated molecular mechanism of LPS tolerance in macrophages, Mouse peritoneal macrophages pre-exposed to LPS exhibited reduced production of inflammatory cytokines in a time- and dose-dependent manner. Activation of neither IL-1 receptor-associated kinase nor NF-kappa B was observed in macrophages that became tolerant by LPS pretreatment, indicating that the proximal event in Toll-like receptor 4 (TLR4)-MyD88-dependent signaling is affected in tolerant macrophages. Although TLR4 mRNA expression significantly decreased within a few hours of LPS pretreatment and returned to the original level at 24 h, the surface TLR4 expression began to decrease within 1 h, with a gradual decrease after that, and remained suppressed over 24 h, A decrease in inflammatory cytokine production in tolerant macrophages well correlates with down-regulation of the surface TLR4 expression, which may explain one of the mechanisms for LPS tolerance.