Effect of perfluorooctane sulphonate-induced Kupffer cell activation on hepatocyte proliferation through the NF-?B/TNF-?/IL-6-dependent pathway

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 characterised. 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??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-? (TNF-?) 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-? 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-? or anti-IL6 treatment. Furthermore, blockage of TNF-? 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-?B inhibitor (PDTC) and c-Jun amino-terminal kinase (JNK)

inhibitor (SP600125) significantly inhibited production of PFOS-induced TNF-? and IL-6. Taken together, these data suggest that PFOS induces Kupffer cell activation, leading to hepatocyte proliferation by through the NF-?B/TNF-?/IL-6-dependent pathway.

Authors: Han R, Zhang F, Wan C, Liu L, Zhong Q, Ding W. ; Full Source: Chemosphere. 2018 Jun; 200:283-294. doi: 10.1016/j.chemosphere.2018.02.137. Epub 2018 Feb 23.

Posted in Uncategorized