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The present study was designed to examine a synergistic role for Interleukin-6 (IL-6) and MSCs therapy in the recovery of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) induced injured hepatocytes in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Injury was induced through 3 mM and 5 mM CCl<jats:sub>4<\/jats:sub>treatment of cultured hepatocytes while fibrotic mouse model was established by injecting 0.5 ml\/kg CCl<jats:sub>4<\/jats:sub>followed by treatment with IL-6 and MSCs<jats:sub>.<\/jats:sub>Effect of MSCs and IL-6 treatment on injured hepatocytes was determined by lactate dehydrogenase release, RT-PCR for (<jats:italic>Bax, Bcl-xl, Caspase3, Cytokeratin 8, NF\u03baB, TNF-\u03b1<\/jats:italic>) and annexin V apoptotic detection. Analysis of MSC and IL-6 treatment on liver fibrosis was measured by histopathology, PAS, TUNEL and Sirius red staining, RT-PCR, and liver function tests for Bilirubin and Alkaline Phosphatase (ALP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant reduction in LDH release and apoptosis was observed in hepatocytes treated with a combination of MSCs and IL-6 concomitant with upregulation of anti-apoptotic gene<jats:italic>Bcl-xl<\/jats:italic>expression and down regulation of<jats:italic>bax, caspase3, NF\u03baB<\/jats:italic>and<jats:italic>TNF-\u03b1<\/jats:italic>. Adoptive transfer of MSCs in fibrotic liver pretreated with IL-6 resulted increased MSCs homing and reduced fibrosis and apoptosis. Hepatic functional assessment demonstrated reduced serum levels of Bilirubin and ALP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pretreatment of fibrotic liver with IL-6 improves hepatic microenvironment and primes it for MSC transplantation leading to enhanced reduction of liver injury after fibrosis. Synergistic effect of IL-6 and MSCs seems a favored therapeutic option in attenuation of liver apoptosis and fibrosis accompanied by improved liver function.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1479-5876-11-78","type":"journal-article","created":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T03:14:01Z","timestamp":1364267641000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Mesenchymal stem cells and Interleukin-6 attenuate liver fibrosis in mice"],"prefix":"10.1186","volume":"11","author":[{"given":"Ghazanfar Ali","family":"Nasir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Mohsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsin","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulaiman","family":"Shams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gibran","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaheen N","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh","family":"Riazuddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,3,26]]},"reference":[{"issue":"3","key":"1486_CR1","first-page":"264","volume":"7","author":"JF Zheng","year":"2008","unstructured":"Zheng JF, Liang LJ: Intra-portal transplantation of bone marrow stromal cells ameliorates liver fibrosis in mice. 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