Preiss S, Thompson A, Chen X, Rodgers S, Markovska V, Desmond P, Visvanathan K, Li K, Locarnini S, Revill P
Research and Molecular Development, Victorian Infectious Disease Reference Laboratories (VIDRL), Melbourne, Australia.
J Viral Hepat. 2008 Dec;15(12):888-900. doi: 10.1111/j.1365-2893.2008.01001.x. Epub 2008 Jul 28.
Hepatitis B virus (HBV) infection is a major cause of liver-related morbidity and mortality. Toll-like receptors (TLRs) have recently been recognized to play an important role in the pathogenesis of chronic hepatitis B (CH-B). Furthermore, manipulation of TLR signalling pathways shows potential as an antiviral therapeutic strategy. Whether hepatocytes themselves possess intact TLR signalling pathways remains controversial. It is critical that cell culture models be developed to allow investigation of the interaction between HBV and the TLR signalling pathways. We have screened three hepatocyte cell lines for the integrity of pro-inflammatory responses and antiviral cytokines following stimulation with interleukin-1 (IL-1) and different TLR ligands. We observed that Huh-7, HepG2 and PH5CH8 cells selectively responded to IL-1 and TLR2 ligands, leading to the activation of NF-kappaB. In addition, the PH5CH8 cell lines were able to induce type 1 interferon (IFN) via both TLR3 and RIG-I following stimulation with poly I:C, HepG2 cells mounted an IFN response via RIG-I only, whereas Huh-7 cells were unresponsive. We conclude that the hepatocyte cell lines investigated display a repertoire of TLR signalling, albeit limited, suggesting that hepatocytes may themselves play an active role in innate immune responses to viruses such as HBV. Furthermore, particular hepatoma cell lines are suitable for investigating the interaction between HBV and hepatocyte-expressed pattern recognition receptors.
乙型肝炎病毒（HBV）感染是导致肝脏相关发病和死亡的主要原因。Toll样受体（TLR）最近被认为在慢性乙型肝炎（CH-B）的发病机制中起重要作用。此外，操纵TLR信号通路显示出作为抗病毒治疗策略的潜力。肝细胞自身是否拥有完整的TLR信号通路仍存在争议。开发细胞培养模型以研究HBV与TLR信号通路之间的相互作用至关重要。我们筛选了三种肝细胞系，以检测在白细胞介素-1（IL-1）和不同TLR配体刺激后促炎反应和抗病毒细胞因子的完整性。我们观察到，Huh-7、HepG2和PH5CH8细胞对IL-1和TLR2配体有选择性反应，导致核因子κB（NF-κB）激活。此外，在用聚肌苷酸-聚胞苷酸（poly I:C）刺激后，PH5CH8细胞系能够通过TLR3和视黄酸诱导基因I（RIG-I）诱导I型干扰素（IFN），HepG2细胞仅通过RIG-I产生IFN反应，而Huh-7细胞无反应。我们得出结论，所研究的肝细胞系显示出一系列TLR信号，尽管有限，这表明肝细胞自身可能在对HBV等病毒的先天免疫反应中发挥积极作用。此外，特定的肝癌细胞系适合研究HBV与肝细胞表达的模式识别受体之间的相互作用。
