Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, 1-1-1 Hondo Akita-shi, Akita 010-8543, Japan.
Gastroenterol Res Pract. 2010;2010:362847. doi: 10.1155/2010/362847. Epub 2011 Jan 17.
Activation of innate immunity is associated with the development of liver disease, including non-alcoholic fatty liver disease (NAFLD). In the innate immune system, Toll-like receptors (TLRs) are sensors that recognize bacterial and viral components such as lipopolysaccharide, bacterial DNA, and peptidoglycan. Recent data have demonstrated that the liver is exposed to a high load of TLR ligands due to bacterial overgrowth and increased intestinal permeability in NAFLD. Upon stimulation by these TLR ligands, hepatic immune cells produce various mediators that are involved in host defense. On the other hand, these mediators alter lipid metabolism, insulin signaling, and cell survival. Indeed, some TLR-deficient mice demonstrate lesser degrees of NAFLD even though TLR ligands are increased. This paper will highlight the recent progress on the study of TLR signaling and their downstream molecules in the development of NAFLD.
先天免疫的激活与肝脏疾病的发展有关，包括非酒精性脂肪性肝病（NAFLD）。在先天免疫系统中，Toll 样受体（TLR）是识别细菌和病毒成分（如脂多糖、细菌 DNA 和肽聚糖）的传感器。最近的数据表明，由于 NAFLD 中细菌过度生长和肠道通透性增加，肝脏暴露于大量 TLR 配体中。这些 TLR 配体刺激后，肝免疫细胞产生各种参与宿主防御的介质。另一方面，这些介质改变脂质代谢、胰岛素信号和细胞存活。事实上，一些 TLR 缺陷型小鼠即使 TLR 配体增加，其 NAFLD 的程度也较轻。本文将重点介绍 TLR 信号及其下游分子在 NAFLD 发展中的最新研究进展。
