Department of Physiology, University of Lausanne, Rue du Bugnon 7, 1005 Lausanne, Switzerland.
Int J Endocrinol. 2013;2013:972962. doi: 10.1155/2013/972962. Epub 2013 Apr 24.
Single-nucleotide polymorphisms within major histocompatibility class II (MHC II) genes have been associated with an increased risk of drug-induced liver injury. However, it has never been addressed whether the MHC II pathway plays an important role in the development of nonalcoholic fatty liver disease, the most common form of liver disease. We used a mouse model that has a complete knockdown of genes in the MHC II pathway (MHCII(Δ/Δ)). Firstly we studied the effect of high-fat diet-induced hepatic inflammation in these mice. Secondly we studied the development of carbon-tetra-chloride- (CCl4-) induced hepatic cirrhosis. After the high-fat diet, both groups developed obesity and hepatic steatosis with a similar degree of hepatic inflammation, suggesting no impact of the knockdown of MHC II on high-fat diet-induced inflammation in mice. In the second study, we confirmed that the CCl4 injection significantly upregulated the MHC II genes in wild-type mice. The CCl4 treatment significantly induced genes related to the fibrosis formation in wild-type mice, whereas this was lower in MHCII(Δ/Δ) mice. The liver histology, however, showed no detectable difference between groups, suggesting that the MHC II pathway is not required for the development of hepatic fibrosis induced by CCl4.
主要组织相容性复合体 II (MHC II) 基因中的单核苷酸多态性与药物性肝损伤的风险增加有关。然而，MHC II 途径是否在非酒精性脂肪性肝病（最常见的肝病形式）的发展中起重要作用，这一点从未得到解决。我们使用了一种 MHC II 途径基因完全敲低的小鼠模型（MHCII(Δ/Δ)）。首先，我们研究了高脂肪饮食诱导的肝内炎症在这些小鼠中的作用。其次，我们研究了四氯化碳（CCl4）诱导的肝纤维化的发展。在高脂肪饮食后，两组均发生肥胖和肝脂肪变性，伴有相似程度的肝炎症，提示 MHC II 的敲低对高脂肪饮食诱导的小鼠炎症没有影响。在第二项研究中，我们证实 CCl4 注射显著上调了野生型小鼠的 MHC II 基因。CCl4 处理显著诱导了野生型小鼠中与纤维化形成相关的基因，而 MHCII(Δ/Δ) 小鼠中的这些基因水平较低。然而，肝组织学检查显示两组之间没有可检测到的差异，表明 MHC II 途径不是 CCl4 诱导的肝纤维化发展所必需的。
