Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease.
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 microm (PM(2.5)) is a risk factor for arteriosclerosis and lung disease, but its effect on NAFLD is unknown. PM(2.5) induces 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 PM(2.5) exposure 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 PM(2.5) exposure may be a significant risk factor for NAFLD progression.
Tan
Hui-Hui
HH
Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA.
Fiel
M Isabel
MI
Sun
Qinghua
Q
Guo
Jinsheng
J
Gordon
Ronald E
RE
Chen
Lung-Chi
LC
Friedman
Scott L
SL
Odin
Joseph A
JA
Allina
Jorge
J
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D019570:Inhalation Exposure; D007728:Kupffer Cells / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity*
D000393:Air Pollutants; D052638:Particulate Matter