Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease.

Journal of Leukocyte Biology
Banishree SahaGyongyi Szabo

Abstract

Macrophages play an important role in inflammation and liver injury. In ALD, activated macrophages, including M1 (proinflammatory) and M2 (anti-inflammatory) macrophages, are present in the liver. As KLF4 has been described as a regulator of macrophage polarization, we investigated its role in ALD. Chronic alcohol feeding in C57Bl/6 mice led to increased expression of M1 (TNF-α, MCP1, and IL-1β) and M2 (Arg1, Mrc1, and IL-10) genes and the frequency of CD206+CD163+ M2 macrophages in the liver. KLF4 mRNA and protein levels were increased in the livers of EtFed compared with PF mice. In macrophages, in vivo and in vitro, EtOH increased KLF4 levels, transcriptional activity, and expression of M1 and M2 genes. KLF4 knockdown and overexpression experiments demonstrated alcohol-dependent and -independent functions of KLF4 in regulating M1 and M2 markers. KLF4 siRNA treatment, alone and in synergy with alcohol, increased the levels of M1 markers. In contrast, KLF4 overexpression increased the levels of M2 and decreased M1 markers, and this was enhanced further by alcohol. KLF4 was regulated by alcohol and its metabolites. KLF4 mRNA and activity were increased in the presence of 4-MP, an inhibitor of ADH, and CYP2E1. However, inhibitio...Continue Reading

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Citations

Jun 23, 2016·Cell Stress & Chaperones·Bao-Ge QuWen-Juan Hu
Sep 24, 2016·Basic Research in Cardiology·Zewei SunLiangrong Zheng
Aug 6, 2016·Scandinavian Journal of Immunology·Y-Y SunJ Li
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Dec 19, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Banishree SahaGyongyi Szabo
Aug 5, 2018·Journal of Cellular Physiology·Tao XuJun Li
Feb 16, 2019·Current Stem Cell Research & Therapy·Lingbo KongDingjun Hao
Jun 28, 2019·Frontiers in Immunology·Sha LiYibin Feng
Apr 20, 2021·Frontiers in Immunology·Arjuna Singanayagam, Evangelos Triantafyllou
Apr 29, 2021·Antioxidants & Redox Signaling·Xiaocheng Charlie DongHyeong Geug Kim
Aug 10, 2021·International Immunopharmacology·Wenyan ChenGuanghong Yang

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