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Front Pharmacol. 2020 Feb 04;11:10. doi: 10.3389/fphar.2020.00010. eCollection 2020.

TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis .

Frontiers in pharmacology

Yue-Meng Wan, Hua-Mei Wu, Yu-Hua Li, Zhi-Yuan Xu, Jin-Hui Yang, Chang Liu, Yue-Feng He, Men-Jie Wang, Xi-Nan Wu, Yuan Zhang

Affiliations

  1. Gastroenterology Department, the 2nd Affiliated Hospital of Kunming Medical University, Kunming, China.
  2. Department of Occupational, Labor and Environmental Health, Public Health Institute of Kunming Medical University, Kunming, China.
  3. The Biomedical Engineering Research Center, Kunming Medical University, Kunming, China.

PMID: 32116692 PMCID: PMC7010862 DOI: 10.3389/fphar.2020.00010

Abstract

Tumor necrosis factor (TNF)-α-stimulated protein 6 (TSG-6) is a secreted protein with diverse tissue protective and anti-inflammatory properties. We aimed to investigate its effective in treating mice with alcoholic hepatitis (AH) and the associated mechanisms. AH was induced in 8-10 week female C57BL/6N mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) injection of recombinant mouse TSG-6 or saline were performed in mice on day 10. Blood samples and hepatic tissues were collected on day 11. Biochemistry, liver histology, flow cytometry, and cytokine measurements were conducted. Compared to the normal control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic macrophage infiltration, serum and hepatic interleukin (IL)-6, and tumor necrosis factor (TNF)-α, which were markedly reduced by i.p. injection of rmTSG-6. Compared to the normal control mice, the hepatic glutathione (GSH), accumulation of M2 macrophages, serum, and hepatic IL-10 and TSG-6 were prominently reduced in the AH mice, which were significantly enhanced after i.p. injection of rmTSG-6. Compared to the normal control mice, hepatic activation of signal transducer and activator of transcription 3 (STAT3) was significantly induced, which was markedly suppressed by rmTSG-6 treatment. TSG-6 were effective for the treatment of AH mice, which might be associated with its ability in inhibiting hepatic oxidative stress and inducing hepatic M2 macrophages polarization

Copyright © 2020 Wan, Wu, Li, Xu, Yang, Liu, He, Wang, Wu and Zhang.

Keywords: STAT3 activation; TSG-6; alcoholic hepatitis; macrophage polarization; oxidative stress

References

  1. Stem Cell Res Ther. 2018 Apr 6;9(1):91 - PubMed
  2. Nat Rev Gastroenterol Hepatol. 2015 Apr;12(4):231-42 - PubMed
  3. J Periodontol. 2015 Jan;86(1):62-71 - PubMed
  4. Hepatology. 2010 Oct;52(4):1291-300 - PubMed
  5. Alcohol. 2007 Jun;41(4):271-80 - PubMed
  6. Alcohol. 2004 Aug;34(1):59-65 - PubMed
  7. PLoS One. 2016 Nov 28;11(11):e0166956 - PubMed
  8. J Cell Physiol. 2018 Sep;233(9):6425-6440 - PubMed
  9. Gastroenterology. 2016 Jun;150(8):1786-97 - PubMed
  10. Stem Cell Res Ther. 2015 Mar 11;6:20 - PubMed
  11. J Neuroinflammation. 2018 Aug 20;15(1):231 - PubMed
  12. Alcohol Clin Exp Res. 2014 Jun;38(6):1520-31 - PubMed
  13. Semin Liver Dis. 1986 Aug;6(3):221-32 - PubMed
  14. Gut. 2006 Aug;55(8):1188-96 - PubMed
  15. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8151-E8158 - PubMed
  16. Matrix Biol. 2019 May;78-79:60-83 - PubMed
  17. J Exp Med. 2003 Nov 17;198(10):1517-25 - PubMed
  18. Biomedicines. 2019 Sep 05;7(3): - PubMed
  19. Nat Rev Immunol. 2011 Oct 14;11(11):723-37 - PubMed
  20. Hepatology. 2010 Jan;51(1):307-28 - PubMed
  21. Alcohol. 2002 May;27(1):53-61 - PubMed
  22. J Hepatol. 2017 Jan;66(1):195-211 - PubMed
  23. Am J Gastroenterol. 2010 Jan;105(1):14-32; quiz 33 - PubMed
  24. Neurobiol Dis. 2013 Nov;59:86-99 - PubMed
  25. J Hepatol. 2012 Aug;57(2):399-420 - PubMed
  26. Int J Biol Sci. 2011 Apr 27;7(5):536-50 - PubMed
  27. Gastroenterology. 2008 Apr;134(4):1148-58 - PubMed
  28. J Hepatol. 2013 Feb;58(2):395-8 - PubMed
  29. Sci Rep. 2016 Jan 04;6:18685 - PubMed
  30. Hepatology. 2013 Nov;58(5):1814-23 - PubMed

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