Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease

Abstract

Due 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 (PM 2.5 ) is a risk factor for arteriosclerosis as well as lung disease, but its effect on NAFLD is unknown. PM 2.5 induces pulmonary dysfunction via toll-like receptor activation on alveolar macrophages. Toll-like receptor 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 progression of NAFLD. Thus, following exposure of male C57BL/6 mice fed high fat chow to concentrated air particulate matter (CAPs) or filtered air for 6 wk, progression of NAFLD was evaluated by standardized histological assessment of hepatic inflammation and fibrosis. In mice fed high fat chow, 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 CAPsexposed mice (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). Conclusion: Ambient PM 2.5 exposure may be a significant risk factor for NAFLD progression.

Evaluation of the Effects of Airborne Particulate Matter on Bone Marrow-Mesenchymal Stem Cells (BM-MSCs): Cellular, Molecular and Systems Biological Approaches

“…This was in tandem with our current gene expression analysis, which showed increased expression of inflammatory cytokines namely TNF-α and IL-6 following exposure to both PM2.5 and PM10. These results are in agreement with a previously reported studies in which PM2.5-10 increased the expression levels of the inflammatory markers including TNF-α and IL-1β in endothelial progenitor cells [37], IL-6 and IL-8 in monocytes [38], IL-6 in Kupffer cells [39] and TNF-α, IL-6 and IL-8 in lung epithelial cells [40]. The mechanism through which the airborne particulates induced apoptosis and increased the expression level of the inflammatory markers was attributed to triggering the formation of the reactive oxygen species (ROS) [37,40,41].…”

Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models

“…Recent studies showed that PM 2.5 exposure activates Kupffer cells in murine liver tissues, indicating that PM 2.5 represents a risk factor for NAFLD progression [1, 10, 13]. In this study, we used a “real-world” PM 2.5 exposure system, “Ohio’s Air Pollution Exposure System for the Interrogation of Systemic Effects (OASIS)”, to perform whole-body exposure of mice to environmentally relevant PM 2.5 .…”

Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet

“…In addition to genetic and diet-related factors, exposure to environmental pollutants has been shown to negatively affect key pathogenic events implicated in NAFLD. For instance, chronic inhalation of low levels of ambient air particulate matter (PM 2.5) has been was reported to induce hepatic steatosis and lipid peroxidation and, moreover, increase hepatic inflammatory and fibrosis stage in mice (Tomaru et al 2007, Tan et al 2009). Exposure to nitrosamines and nicotine has also been found to play critical roles in the pathogenesis of NAFLD (Tong et al 2009, Azzalini et al 2010, Friedman et al 2012.…”