Zhen Wang1, Xiaoxia Zhang2, Lili Zhu3, Xiaoli Yang4, Fang He5, Ting Wang3, Ting Bao4, Haixia Lu4, Hao Wang6, Shaoqi Yang7. 1. Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China; Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China. 2. College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China. 3. Department of Pathogenic Biology and Medical Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, China. 4. Clinical Medical College, Ningxia Medical University, Yinchuan 750004, Ningxia, China. 5. Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China. 6. Department of Pathogenic Biology and Medical Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, China. Electronic address: wanghaograduate@126.com. 7. Department of Gastroenterology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China. Electronic address: shaoqiynh@163.com.
Abstract
BACKGROUND: Alcoholic liver disease (ALD) presents one of the leading causes of cirrhosis worldwide. We have demonstrated that inulin alleviates ALD in mice. However, the exact role of hepatic macrophages in effects of inulin on ALD remains largely unclear. METHODS: In vivo, mice were divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with inulin (INU) group (PF/INU) and AF with INU group (AF/INU). Each group was fed modified Lieber-DeCarli liquid diet with or without alcohol. In vitro, RAW264.7 cell lines were polarized to M1 macrophage (Mψ) or M2 Mψ subsets with lipopolysaccharide (LPS) or interleukin-4 (IL-4) stimulation, respectively. The effects of propionate, butyrate and valeric on macrophage M1/M2 were investigated. RESULTS: The contents of propionate, butyrate and valeric were significantly increased in AF/INU group compared with that in the AF/CON group. M1 Mψ, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in AF/INU group were significantly lower than those in AF/CON group. In contrast, M2 Mψ, arginase-1 (Arg-1), and interleukin-10 (IL-10) were notably increased in AF/INU group. In vitro, sodium propionate, sodium butyrate and sodium valerate can suppress M1 Mψ and increase M2 Mψ polarization. CONCLUSION: In ALD, inulin ameliorates the inflammation via SCFAs-inducing suppression of M1 and facilitation of M2 Mψ, which may potentially contribute to the control of the disease.
BACKGROUND:Alcoholic liver disease (ALD) presents one of the leading causes of cirrhosis worldwide. We have demonstrated that inulin alleviates ALD in mice. However, the exact role of hepatic macrophages in effects of inulin on ALD remains largely unclear. METHODS: In vivo, mice were divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with inulin (INU) group (PF/INU) and AF with INU group (AF/INU). Each group was fed modified Lieber-DeCarli liquid diet with or without alcohol. In vitro, RAW264.7 cell lines were polarized to M1 macrophage (Mψ) or M2 Mψ subsets with lipopolysaccharide (LPS) or interleukin-4 (IL-4) stimulation, respectively. The effects of propionate, butyrate and valeric on macrophage M1/M2 were investigated. RESULTS: The contents of propionate, butyrate and valeric were significantly increased in AF/INU group compared with that in the AF/CON group. M1 Mψ, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in AF/INU group were significantly lower than those in AF/CON group. In contrast, M2 Mψ, arginase-1 (Arg-1), and interleukin-10 (IL-10) were notably increased in AF/INU group. In vitro, sodium propionate, sodium butyrate and sodium valerate can suppress M1 Mψ and increase M2 Mψ polarization. CONCLUSION: In ALD, inulin ameliorates the inflammation via SCFAs-inducing suppression of M1 and facilitation of M2 Mψ, which may potentially contribute to the control of the disease.