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Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38\u03b1 plays a regulatory role in the tissue repair following <jats:sc>d<\/jats:sc>\u2010galactosamine (GalN)\/tumor necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1)\u2010induced acute liver injury. We found that macrophage p38\u03b1\u2010deficient 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\/<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide\/interferon\u2010\u03b3 treatment but not by inteleukin\u20104 stimulation, while pharmaceutical inhibition of p38\u03b1 induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38\u03b1 signaling is involved in the pathogenesis of liver injury induced by GalN\/<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, and inhibition of p38\u03b1 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.<\/jats:p>","DOI":"10.1111\/febs.14294","type":"journal-article","created":{"date-parts":[[2017,10,20]],"date-time":"2017-10-20T09:32:40Z","timestamp":1508491960000},"page":"4200-4215","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Deficiency of p38\u03b1 in macrophage ameliorates <scp>d<\/scp>\u2010galactosamine\/<scp>TNF<\/scp>\u2010\u03b1\u2010induced acute liver injury in mice"],"prefix":"10.1111","volume":"284","author":[{"given":"Jiao","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchao","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Food Safety Research Institute for Nutritional Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences 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