Effect of perfluorooctane sulphonate-induced Kupffer cell activation on hepatocyte proliferation through the NF-κB/TNF-α/IL-6-dependent pathway. (June 2018)

• Record Type: Journal Article
• Authors: Han, Rui; Zhang, Fang; Wan, Chong; Liu, Limin; Zhong, Qiang; Ding, Wenjun
• Is Part Of: Chemosphere. Volume 200(2018)
• Page Start: 283
• Page End: 294
• Publication Date: 2018-06
• Subjects: PFOS -- Kupffer cells -- Inflammation -- Hepatocyte proliferation -- NF-κB/ TNF-?/IL-6; ALT alanine aminotransferase -- AST aspartate transaminase -- APAP acetaminophen -- CCl4 carbon tetrachloride -- CHE cholinesterase -- CM conditioned media -- CyD1 Cyclin D1 -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM Dulbecco's modified Eagle's medium -- EdU 5-ethynyl-20-deoxyuridine -- ELISA enzyme linked immunosorbent assay -- GdCl3 gadolinium chloride -- GP130 IL-6 signal transducer -- HCs hepatocytes -- IκB inhibitor of NF-κB -- IL-1 interleukin-1 -- IL-6 interleukin-6 -- IL-10 interleukin-10 -- IL-1β interleukin 1β -- JNK c-Jun amino-terminal kinase -- KCs Kupffer cells -- LPS lipopolysaccharide -- NEAA non-essential amino acids -- NF-κB transcription factor nuclear factor-κB -- PBS phosphate buffered saline -- PFASs polyfluoroalkyl chemicals -- PFOA perfluorooctanoate -- PFOS perfluorooctane sulphonate -- PCNA proliferating cell nuclear antigen -- PI propidium iodide -- SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis -- TBA thiobarbituric acid -- TNF-ɑ tumour necrosis factor-ɑ -- TNFR tumour necrosis factor receptor; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2018.02.137
• Languages: English
• ISSNs: 0045-6535

Abstract

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 10 mg/kg body weight) for 28 days. Rat primary cultured Kupffer cells or hepatocytes were exposed to 100 μM 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-ɑ (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-ɑ/IL-6-dependent pathway. Highlights: PFOS exposure induces Kupffer cell activation in the liver of rats. PFOS increased the inflammatory cytokines in serum of rats and Kupffer cells. PFOS induced hepatocyte proliferation via the inflammatory-mediated NF-κB/TNF-ɑ/IL-6 pathway.