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We have shown that <jats:italic>in vitro<\/jats:italic> activated stellate cells increase their expression of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 as well as the receptor <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 and that receptor engagement promotes a profibrogenic phenotype. Furthermore, injury promotes increased hepatic expression of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 and a massive infiltration of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4\u2010expressing leukocytes, granulocytes and myeloid cells. The primary site of inflammatory cell accumulation is around the <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12\u2010rich portal tracts and within fibrotic septae, indicating a role for <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 during injury. In order to characterize the relevance of the <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4\/<jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 chemokine axis during hepatic injury we inhibited the axis using <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>3100, a <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4 small molecule inhibitor, in models of chronic and acute liver injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were subjected to acute and chronic <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> liver injury with and without <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>3100 administration. The degree of liver injury, fibrosis and the composition of the intrahepatic inflammatory response were characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment of mice with <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>3100 in the chronic <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub> model of liver injury led to an increase in hepatic inflammation and fibrosis with a specific increase in intrahepatic neutrophils. Furthermore, in an acute model of <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>l<jats:sub>4<\/jats:sub>\u2010induced liver injury, <jats:styled-content style=\"fixed-case\">AMD<\/jats:styled-content>3100 led to an increase in the number of intrahepatic neutrophils and a trend towards worse necrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Together, this data suggests that inhibition of the <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>4\/<jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>12 chemokine axis is injurious through modulation of the hepatic inflammatory response and that this axis may serve a protective role in liver injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.12411","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T06:56:46Z","timestamp":1409209006000},"page":"794-803","source":"Crossref","is-referenced-by-count":35,"title":["Inhibition of the <scp>CXCL<\/scp>12\/<scp>CXCR<\/scp>4 chemokine axis with <scp>AMD<\/scp>3100, a <scp>CXCR<\/scp>4 small molecule inhibitor, worsens murine hepatic injury"],"prefix":"10.1111","volume":"45","author":[{"given":"Yedidya","family":"Saiman","sequence":"first","affiliation":[{"name":"Division of Liver Diseases Department of Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JingJing","family":"Jiao","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases Department of Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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