Cutting Edge: Endotoxin Tolerance in Mouse Peritoneal Macrophages Correlates with Down-Regulation of Surface Toll-Like Receptor 4 Expression

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作者：

F Nomura，S Akashi，Y Sakao，S Sato，T Kawai，M Matsumoto，K Nakanishi，M Kimoto，K Miyake，K Takeda

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摘要：

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. 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-kappaB was observed in macrophages that became tolerant by LPS pretreatment, indicating that the proximal event in Toll-like receptor 4 ()-MyD88-dependent signaling is affected in tolerant macrophages. Although expression significantly decreased within a few hours of LPS pretreatment and returned to the original level at 24 h, the surface expression began to decrease within 1 h, with a gradual decrease after that, and remained suppressed over 24 h. A decrease in inflammatory in tolerant macrophages well correlates with down-regulation of the surface expression, which may explain one of the mechanisms for LPS tolerance.

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关键词：

Cell Membrane Macrophages, Peritoneal Animals Mice, Inbred C57BL Mice Lipopolysaccharides Membrane Glycoproteins Drosophila Proteins Receptors, Cell Surface Interleukin-6