Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8851680 | Chemosphere | 2018 | 48 Pages |
Abstract
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 10â¯mg/kg body weight) for 28 days. Rat primary cultured Kupffer cells or hepatocytes were exposed to 100â¯Î¼M PFOS for 0-48â¯h. Our results showed that PFOS exposure caused serious hepatocellular damage and obvious inflammatory cell infiltration and increased serum tumour necrosis factor-É (TNF-α) 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 D1 (CyD1) in liver. In vitro, PFOS significantly induced production of TNF-α 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-TNF-α or anti-IL6 treatment. Furthermore, blockage of TNF-α 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-κB inhibitor (PDTC) and c-Jun amino-terminal kinase (JNK) inhibitor (SP600125) significantly inhibited production of PFOS-induced TNF-α and IL-6. Taken together, these data suggest that PFOS induces Kupffer cell activation, leading to hepatocyte proliferation by through the NF-κB/TNF-É/IL-6-dependent pathway.
Keywords
TBAIκBIL-1βPFASsIL-10DAPIHCsAPAPCCl4ALTCyclin D1gp130KCSTNFRPFOSIL-1NF-κBPCNAPerfluorooctane sulphonatePBSNEAAc-jun amino-terminal kinaseLPSIL-6DMEMGdCl3JnkPFOA4′,6-diamidino-2-phenylindoleEdUHepatocytesDulbecco's modified Eagle's mediumASTAlanine aminotransferaseProliferating Cell Nuclear Antigenenzyme linked immunosorbent assayAcetaminophennon-essential amino acidsThiobarbituric acidinflammationSDS-PAGEsodium dodecyl sulphate polyacrylamide gel electrophoresisHepatocyte proliferationInterleukin-10interleukin 1βinterleukin-6interleukin-1aspartate transaminaseELISAconditioned mediaKupffer cellsPhosphate buffered salinePerfluorooctanoatelipopolysaccharideinhibitor of NF-κBPolyfluoroalkyl chemicalsPropidium iodideCarbon tetrachlorideCHECholinesterasegadolinium chloridetumour necrosis factor receptor
Related Topics
Life Sciences
Environmental Science
Environmental Chemistry
Authors
Rui Han, Fang Zhang, Chong Wan, Limin Liu, Qiang Zhong, Wenjun Ding,