Deficiency of p38α in macrophage ameliorates d‐galactosamine/TNF‐α‐induced acute liver injury in mice. (14th November 2017)

• Record Type: Journal Article
• Authors: Liu, Jiao; Zhang, Shengjie; Cao, Hongchao; Wang, Hui; Sun, Chao; Liu, Shengnan; Yu, Shuxian; Li, Yan; Liu, Wei; Wang, Hui; Jiang, Jingjing; Ying, Hao
• Is Part Of: FEBS journal. Volume 284:Number 24(2017)
• Page Start: 4200
• Page End: 4215
• Publication Date: 2017-11-14
• Subjects: liver injury -- macrophage polarization -- p38α; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14294
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38α plays a regulatory role in the tissue repair followingd ‐galactosamine (GalN)/tumor necrosis factor‐α (TNF‐α)‐induced acute liver injury. We found that macrophage p38α‐deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF‐α treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon‐γ treatment but not by inteleukin‐4 stimulation, while pharmaceutical inhibition of p38α induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38α signaling is involved in the pathogenesis of liver injury induced by GalN/TNF‐α, and inhibition of p38α signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype. Abstract : Hepatic macrophages promote tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells and promoting hepatocyte proliferation. Hao Ying and colleagues report that the targeted deletion of p38α in macrophages is beneficial in mouse models of liver injury. They found that lipopolysaccharide/interferon‐γ treatment induces p38α activation in macrophages, activating CREB–C/EBPβ signalling and a subsequent inflammatory response. Lack of p38α induced a shift in polarization from M1 to M2 macrophages, resulting in decreased apoptosis and inflammation, and accelerated liver regeneration.