Keming Li1,2, Qian Zhao1, Ziyan Fan3, Shouyin Jia1, Qing Liu4, Fengyan Liu5, Shili Liu6. 1. Department of Medical Microbiology, School of Basic Medical Science & Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China. 2. Shandong Academy of Chinese Medicine, No. 7 Yanzishanxi Road, Jinan, 250013, Shandong, China. 3. China National Tobacco Quality Supervision and Test Center, Zhengzhou, 450001, Henan, China. 4. Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. 5. The Second Hospital of Shandong University, Jinan, 250012, Shandong, China. 6. Department of Medical Microbiology, School of Basic Medical Science & Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China. liushili@sdu.edu.cn.
Abstract
BACKGROUND: Perfluorodecanoic acid (PFDA) is a type of perfluoroalkyl acid (PFAA). PFDA has toxicity similar to dioxin; its effect on the body is not through a single target or a single pathway. However, the mechanism at the global level is still unclear. METHODS AND RESULTS: We treated mice with PFDA and characterized the global changes in gene expression in the liver using microarray analyses. The enriched KEGG pathways and GO analyses revealed that PFDA greatly affected the immune response, which was different from the response of gastric cells previously studied. As a proof of principle, the expressions of IL-1β and IL-18 were both decreased after PFDA treatment, and qRT-PCR and ELISAs verified the reduction of IL-1β and IL-18 in liver tissues. Mechanistic investigations indicated that PFDA inhibited caspase-1 activation, and decreased the mRNA levels of NLRP1, NLRP3, and NLRC4; thus, suggesting that inflammasome assemblies were suppressed. Further microarray data revealed that cIAP2 and its binding proteins, which are critical for regulating inflammasome assembly, were also repressed by PFDA. In addition, flow cytometry results revealed a significant inhibition of Th1 cell differentiation in the livers of PFDA-treated mice. CONCLUSIONS: The results of this study suggested that one of the main toxic effects of PFDA on livers was the inhibition of immune response.
BACKGROUND: Perfluorodecanoic acid (PFDA) is a type of perfluoroalkyl acid (PFAA). PFDA has toxicity similar to dioxin; its effect on the body is not through a single target or a single pathway. However, the mechanism at the global level is still unclear. METHODS AND RESULTS: We treated mice with PFDA and characterized the global changes in gene expression in the liver using microarray analyses. The enriched KEGG pathways and GO analyses revealed that PFDA greatly affected the immune response, which was different from the response of gastric cells previously studied. As a proof of principle, the expressions of IL-1β and IL-18 were both decreased after PFDA treatment, and qRT-PCR and ELISAs verified the reduction of IL-1β and IL-18 in liver tissues. Mechanistic investigations indicated that PFDA inhibited caspase-1 activation, and decreased the mRNA levels of NLRP1, NLRP3, and NLRC4; thus, suggesting that inflammasome assemblies were suppressed. Further microarray data revealed that cIAP2 and its binding proteins, which are critical for regulating inflammasome assembly, were also repressed by PFDA. In addition, flow cytometry results revealed a significant inhibition of Th1 cell differentiation in the livers of PFDA-treated mice. CONCLUSIONS: The results of this study suggested that one of the main toxic effects of PFDA on livers was the inhibition of immune response.
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