乙型肝炎病毒颗粒优选诱导Kupffer细胞产生TGF-β1而不是促炎细胞因子
Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-β1 over pro-inflammatory cytokines
Kupffers细胞是驻留在肝脏的巨噬细胞；占肝细胞总数的15%，主要的作用是清除门静脉中的颗粒物质；
背景
Kupffer细胞和相关细胞因子被认为在肝纤维化中起关键作用;然而，Kupffer细胞在乙型肝炎病毒相关纤维化发生中所起的作用尚不清楚。
方法
原代大鼠Kupffer细胞培养上清液中不同滴度的乙型肝炎病毒颗粒和转化生长因子（TGF）-β1，白细胞介素（IL）-1，IL-6和肿瘤坏死因子（TNF）-α的浓度每24小时测量7天。还分别使用定量实时聚合酶链反应和蛋白质印迹分析了库普弗细胞中这些细胞因子的mRNA和蛋白质水平。
结果
在7天暴露于乙型肝炎病毒期间，Kupffer细胞维持正常的形态和功能。乙型肝炎病毒刺激的Kupffer细胞分泌的TGF-β1浓度（6 log IU / ml乙型肝炎病毒）分别在第3天和第7天增加5.38和7.75倍（p <0.01）。蛋白质印迹显示暴露于高滴度乙型肝炎病毒的Kupffer细胞中TGF-β1的表达分别在第3天和第7天增加1.80倍和2.42倍（p <0.01）。相反，在整个实验中，Kupffer细胞表达和促炎细胞因子（IL-6，IL-1和TNF-α）的分泌未改变。
结论
乙型肝炎病毒优先刺激Kupffer细胞产生促纤维化/抗炎细胞因子TGF-β1而不是促炎细胞因子IL-6，IL-1和TNF-α。这可能部分解释了为什么在只有最小或没有坏死性炎症的慢性乙型肝炎病毒感染的病例中仍然存在明显的肝纤维化。
Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-β1 over pro-inflammatory cytokines
Liver, Pancreas and Bilary Tract
Background
Kupffer cells and related cytokines are thought to play a critical role in liver fibrosis; however, the role played by Kupffer cells in hepatitis B virus-related fibrogenesis is unknown.
Methods
Primary rat Kupffer cells were cultured with different titres of hepatitis B virus particles and the concentrations of transforming growth factor (TGF)-β1, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α in the culture supernatant were measured every 24 h for 7 days. The mRNA and protein levels of these cytokines in Kupffer cells were also analysed using quantitative real-time polymerase chain reaction and western blotting, respectively.
Results
Kupffer cells maintained normal morphology and function throughout the 7-day exposure to hepatitis B virus. The concentration of TGF-β1 secreted by hepatitis B virus-stimulated Kupffer cells (6 log IU/ml hepatitis B virus) increased 5.38- and 7.75-fold by Days 3 and 7, respectively (p < 0.01). Western blotting showed that TGF-β1 expression in Kupffer cells exposed to high titres of hepatitis B virus increased 1.80- and 2.42-fold by Days 3 and 7, respectively (p < 0.01). In contrast, Kupffer cell expression and secretion of pro-inflammatory cytokines (IL-6, IL-1 and TNF-α) was unchanged throughout the experiment.
Conclusion
Hepatitis B virus preferentially stimulates Kupffer cells to produce the pro-fibrogenic/anti-inflammatory cytokine TGF-β1 rather than the pro-inflammatory cytokines IL-6, IL-1 and TNF-α. This may partly explain why overt liver fibrosis still presents in cases of chronic hepatitis B virus infection with minimal (or no) necro-inflammation.
Author links open overlay panelHaiLi1Huan-WeiZheng1HuiChenZhi-ZhiXingHongYouMinCongJi-DongJia
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https://doi.org/10.1016/j.dld.2011.11.005Get rights and content
Abstract
Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-β1 over pro-inflammatory cytokines - ScienceDirect https://www.sciencedirect.com/science/article/pii/S1590865811004324