Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.
Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.
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环境空气颗粒物暴露引起的库普弗细胞激活可能会加剧非酒精性脂肪肝。
DOI：
10.1080/15476910903241704
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发表时间：
2009
影响因子：
3.3
通讯作者：
Allina,Jorge
中科院分区：
文献类型：
--
作者：
Tan,Hui-Hui;Fiel,MIsabel;Sun,Qinghua;Guo,Jinsheng;Gordon,RonaldE;Chen,Lung-Chi;Friedman,ScottL;Odin,JosephA;Allina,Jorge
由于肥胖的增加，非酒精性脂肪性肝病（NAFLD）现在是美国最流行的肝病。NAFLD被认为是代谢综合征的一个组成部分，代谢综合征是一组疾病，还包括糖尿病、血脂异常、动脉硬化和高血压。暴露于空气动力学直径< 2.5 μm的环境空气颗粒物（PM2.5）是动脉硬化和肺部疾病的危险因素，但其对NAFLD的影响尚不清楚。PM2.5通过激活肺泡巨噬细胞Toll样受体（TLR）诱导肺功能障碍。库普弗细胞的TLR活化、常驻肝巨噬细胞和随后的促炎细胞因子产生已被证明在NAFLD进展中起关键作用。我们假设PM2.5暴露是NAFLD进展的重要危险因素。因此，在喂食高脂肪食物（HFC）的雄性C57 BL/6小鼠暴露于浓缩空气颗粒物（CAP）或过滤空气6周后，通过肝脏炎症和纤维化的标准化组织学评估来评估NAFLD的进展。在HFC组，CAP组小鼠肝脏炎症程度（3.00 ± 0.00）和纤维化程度（1.00 ± 0.00）均显著高于过滤空气组（1.50 ± 0.71，P < 0.001）和纤维化程度（0.60 ± 0.52，P = 0.023）。CAPs组小鼠含PM的枯否细胞数量增加（2.00 ± 0.94 vs.0.20 ± 0.42，P< 0.001）。PM暴露以剂量依赖性方式使分离的野生型Kupffer细胞而不是TLR 4 −/−Kupffer细胞的IL-6分泌增加7倍（P< 0.050）。总之，环境PM2.5暴露可能是NAFLD进展的重要危险因素。
Owing to increased obesity, non-alcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the United States. NAFLD is considered a component of metabolic syndrome, a cluster of disorders that also includes diabetes mellitus, dyslipidemia, arteriosclerosis, and hypertension. Exposure to ambient air particulate matter with aerodynamic diameters < 2.5 μm (PM2.5) is a risk factor for arteriosclerosis and lung disease, but its effect on NAFLD is unknown. PM2.5induces pulmonary dysfunction via Toll-like receptor (TLR) activation on alveolar macrophages. TLR activation of Kupffer cells, resident hepatic macrophages, and subsequent pro-inflammatory cytokine production have been shown to play a key role in NAFLD progression. We hypothesized that PM2.5exposure is a significant risk factor for the progression of NAFLD. Thus, following exposure of male C57BL/6 mice fed high fat chow (HFC) to concentrated air particulate matter (CAPs) or filtered air for 6 weeks, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed HFC, the hepatic inflammatory grade (3.00 ± 0.00 vs. 1.50 ± 0.71,P< 0.001) and fibrosis stage (1.00 ± 0.00 vs. 0.60 ± 0.52,P= 0.023) were both significantly higher in mice exposed to CAPs versus filtered air, respectively. Increased numbers of Kupffer cells contained PM in CAPs-exposed mice scores of (2.00 ± 0.94 vs. 0.20 ± 0.42, respectively,P< 0.001). PM exposure increased IL-6 secretion up to seven-fold in a dose-dependent manner by isolated wild-type but not TLR4−/−Kupffer cells (P< 0.050). In conclusion, ambient PM2.5exposure may be a significant risk factor for NAFLD progression.