Innate Immune Reactivity of the Ileum–Liver Axis in Nonalcoholic Steatohepatitis
Innate Immune Reactivity of the Ileum–Liver Axis in Nonalcoholic Steatohepatitis
复制标题
DOI：
10.1007/s10620-012-2073-z
复制
发表时间：
2012-02
影响因子：
3.1
通讯作者：
Tatsuhiro Tsujimoto;H. Kawaratani;Toshiyuki Kitazawa;M. Uemura;H. Fukui
中科院分区：
文献类型：
--
作者：
Tatsuhiro Tsujimoto;H. Kawaratani;Toshiyuki Kitazawa;M. Uemura;H. Fukui
背景肠道植物群内革兰氏阴性杆菌的过度增殖和细菌移位以及门静脉内毒素水平的升高参与了非酒精性脂肪性肝炎（NASH）的发生。我们分析了血清和肝脏组织，以评估在这个NASHmodel.ResultsSignificant增加检测到血清ALT水平和门静脉血清和全肝水平的TNF-α和IFN-γ在NASH组的天然免疫反应性的影响。实时荧光定量PCR显示NASH组TNF-α和TLR 4 mRNA表达明显增强。NASH组库普弗细胞培养上清中TNF-α水平明显高于对照组。回肠组织标本的免疫染色导致更大的染色TNF-α，TLR 4，和巨噬细胞/树突状细胞，主要是在粘膜下层，在NASH组比在control group.ConclusionsIn大鼠NASH模型的小肠和肝脏，先天性免疫反应的增强，介导的TLR 4信号，导致TNF-α的产生增加的可能性。小肠和肝脏之间的这种相互作用可能参与NASH的发生和进展。
BackgroundOver-proliferation and bacterial translocation of Gram-negative bacilli within the intestinal flora, and increased portal venous levels of endotoxins, are involved in nonalcoholic steatohepatitis (NASH).AimTo evaluate the innate immune response in the small intestine and liver using the rat NASH model.MethodsWe produced the NASH model by administering a choline-deficient amino acid-defined diet to F344 rats. We analyzed the serum and liver tissue to assess the effects of innate immune reactivity in this NASH model.ResultsSignificant increases were detected in serum ALT levels and in the portal venous serum and whole-liver levels of TNF-α and IFN-γ in the NASH group. Strong Sirius red staining and TNF-α immune staining were seen in the NASH group, and real-time PCR revealed significantly increased expression of TNF-α and TLR4 mRNA in the NASH group. Higher TNF-α levels were detected in the Kupffer cells isolated culture supernatant in the NASH group than in the control group. Immune staining of the ileal tissue specimens resulted in greater staining of TNF-α, TLR4, and macrophage/dendritic cells, mainly in the submucosa, in the NASH group than in the control group.ConclusionsIn the small intestine and liver of the rat NASH model, the possibility that enhancement of the innate immune response, mediated by the TLR4 signal, led to increased production of TNF-α was suggested. This interaction between the small intestine and liver may be involved in the onset and progression of NASH.