Regulation of N-acetylcysteine on peripheral circulatory and hepatic myeloid-derived suppressor cells in non-alcoholic fatty liver disease mice

doi:10.12092/j.issn.1009-2501.2019.09.005

Abstract

Abstract:

AIM: To observe the local and systemic dysregulation of immune cells myeloid-derived suppressor cells (MDSCs) in high fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) mice, and to study the regulation function of N-acetylcysteine (NAC) on MDSCs and associated pro-inflammatory cytokines. METHODS: Thirty male C57B/L6 mice were equally divided into three groups: normal chow diet group (Lean), high fat diet group (HFD) and NAC group (NAC). After 16 weeks, liver pathological change was evaluated by HE and oil red O staining. The levels of MDSCs in peripheral blood and liver tissue were measured through flow cytometry and immunohistochemistry, respectively. The changes of MDSCs secreted pro-inflammatory cytokines S100 calcium-binding protein A8 (S100A8) and S100 calcium-binding proteinA9 (S100A9) in mice liver were tested by real-time quantitative reverse transcription-polymerize chain reaction and western blot. RESULTS:Compared with lean group, HFD group mice exhibited hepatic steatosis and inflammatory cell infiltration. The frequencies of CD11b+Gr-1+ MDSCs in peripheral blood and Gr-1+ cells in liver tissue were elevated in HFD group as well (P<0.01). The mRNA and protein levels of S100A8 and S100A9 also were increased in the livers of HFD group mice (P<0.05). Hepatic steatosis was alleviated and liver-infiltrated inflammatory cells were reduced after NAC treatment. The frequencies of MDSCs in peripheral blood and liver tissue, as well as the levels of S100A8 and S100A9 were decreased by NAC (P<0.05). In addition, NAC effectively suppressed α-SMA level and ameliorated liver fibrosis. CONCLUSION:NAC may slow the progression of NAFLD by regulating MDSCs accumulation, inhibiting inflammation and fibrosis.

Key words: myeloid-derived suppressor cells, N-acetylcysteine, non-alcoholic fatty liver disease, cytokine

CLC Number:

R965.2
R575

WU Jiayuan, ZHENG Li, MO Juanfen, GUO Li, CAO Chenxi, BAO Yi. Regulation of N-acetylcysteine on peripheral circulatory and hepatic myeloid-derived suppressor cells in non-alcoholic fatty liver disease mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(9): 989-996.

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