Endotoxin and cytokine regulation of toll-like receptor (TLR) 2 and TLR4 gene expression in murine liver and hepatocytes
Endotoxin and cytokine regulation of toll-like receptor (TLR) 2 and TLR4 gene expression in murine liver and hepatocytes
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DOI：
10.1089/10799900050163299
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发表时间：
2000-10-01
影响因子：
2.3
通讯作者：
Onozaki, K
中科院分区：
文献类型：
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作者：
Matsumura, T;Ito, A;Onozaki, K
Toll样受体（TLR）2和TLR 4是白细胞介素-1受体（IL-1 R）家族的成员，并且响应于细菌和细菌组分而与IL-1 R类似的信号。在这项研究中，我们研究了它们在小鼠组织中，特别是在肝脏和肝细胞中的基因表达调控。当小鼠被给予脂多糖（LPS）时，TLR 2 mRNA在脑、心、肺、肝和肾中上调。相反，它在脾脏中下调。TLR 4 mRNA在脑内表达减少。在心脏和肺中，它增加了，在肝脏，肾脏和脾脏中没有受到影响。在肝脏和肝细胞中进一步分析TLR mRNA。与LPS处理一样，IL-1、IL-6或肿瘤坏死因子（TNF）的施用上调TLR 2 mRNA。但对TLR 4 mRNA水平无影响。在原代培养的肝细胞中，TLR 2 mRNA被LPS、IL-1或TNF上调，但不被IL-6或地塞米松上调。对TLR 4 mRNA表达无影响。在鼠肝癌细胞系Hepa 1-6中观察到类似的反应。这些结果表明，在感染革兰氏阴性菌，LPS和促炎细胞因子差异调节TLR 2和TLR 4在小鼠肝细胞的基因表达，这可能会导致病理和宿主防御反应的肝脏。
Toll-like receptor (TLR) 2 and TLR4 are members of the interleukin-1 receptor (IL-1R) family and transduce similar signals as IL-1R in response to bacteria and bacterial components. In this study, we investigated the regulation of their gene expression in murine tissues, especially in the liver and hepatocytes. When mice were administered lipopolysaccharide (LPS), TLR2 mRNA was upregulated in the brain, heart, lung, liver, and kidney. In contrast, it was downregulated in the spleen. TLR4 mRNA was decreased in the brain. In the heart and lung, it increased, and it was not affected in the liver, kidney, and spleen. TLR mRNA was further analyzed in the liver and hepatocytes. Like LPS treatment, administration of IL-1, IL-6, or tumor necrosis factor (TNF) upregulated TLR2 mRNA. However, none of them affected the TLR4 mRNA level. In primary cultured hepatocytes, TLR2 mRNA was upregulated by LPS, IL-1, or TNF but not by IL-6 or dexamethasone. None of them affected TLR4 mRNA expression. Similar responses were observed in the murine hepatoma cell line Hepa 1-6. These results suggest that in infection with gram-negative bacteria, LPS and proinflammatory cytokines differentially regulate gene expression of TLR2 and TLR4 in murine hepatocytes, which may lead to pathologic and host defense reactions in the liver.