Journal
CHEMOSPHERE
Volume 200, Issue -, Pages 283-294Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2018.02.137
Keywords
PFOS; Kupffer cells; Inflammation; Hepatocyte proliferation; NF-kappa B/TNF-?/IL-6
Categories
Funding
- National Science and Technology Ministry of China [2007BAC27B02-2]
- National Natural Science Foundation of China [10875170, U1432245, 91643206]
- Gong-Yi Program of China Ministry of Environmental Protection [200909016]
Ask authors/readers for more resources
Perfluorooctane sulfonate (PFOS), one member of polyfluoroalkyl chemicals (PFASs), persist in the environment and are found in relatively high concentrations in animal livers. PFOS has been shown to induce tumour of the liver in rats following chronic dietary administration. However, the molecular mechanisms involved in PFOS-induced hepatocellular hypertrophy are still not well characterized. In this study, male Sprague-Dawley rats were daily gavaged with PFOS (1 or 10 mg/kg body weight) for 28 days. Rat primary cultured Kupffer cells or hepatocytes were exposed to 100 mu M PFOS for 0-48 h. Our results showed that PFOS exposure caused serious hepatocellular damage and obvious inflammatory cell infiltration and increased serum tumour necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) levels. Particularly, PFOS exposure triggered Kupffer cell activation and significantly upregulated the expression of proliferating cell nuclear antigen (PCNA), c-Jun, c-MYC and Cyclin Dl (CyD1) in liver. In vitro, PFOS significantly induced production of TNF-alpha and IL-6 in Kupffer cells and increased PCNA, c-Jun, c-MYC and CyD1 expression in the primary hepatocytes co-cultured with Kupffer cells. However, Kupffer cell activation was mostly abolished by anti-INF-alpha or anti-IL6 treatment. Furthermore, blockage of TNF-alpha and IL-6 significantly inhibited hepatocyte proliferation by gadolinium chloride (GdCl3) pre-treatment in PFOS-treated mice and primary cultured Kupffer cells. On the other hand, NF-kappa B inhibitor (PDTC) and c-Jun amino-terminal kinase (JNK) inhibitor (SP600125) significantly inhibited production of PFOS-induced INF-alpha and IL-6. Taken together, these data suggest that PFOS induces Kupffer cell activation, leading to hepatocyte proliferation by through the NF-kappa B/TNF-alpha/IL-6-dependent pathway. (C) 2018 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available