Conclusions: The DSS-induced mouse colitis may promote hepatic inflammation and fibrosis in mice treated by CCl4. Disclosures: The following people have nothing to disclose: Xiaolan Zhang, Yufeng Liu, Libo Zheng, Guochao Niu, Hong Zhang, Jinbo Guo, Guozun Zhang, Huicong Sun “
“Clinical trials and animal models suggest that infusion of PKC412 bone marrow cells (BMCs) is effective therapy for liver fibrosis,

but the underlying mechanisms are obscure, especially those associated with early effects of BMCs. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMCs showing antifibrotic effects in mice with carbon tetrachloride–induced liver this website fibrosis. An interaction between BMCs and activated hepatic stellate cells (HSCs) was investigated using an in vitro coculturing system. Within 24 hours, infused BMCs were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, and expanded regulatory T cells

but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10–deficient (IL-10−/−) BMCs failed to reproduce these effects in fibrotic livers. Intriguingly, in isolated cells, CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ BMCs expressed more IL-10 after coculturing with activated HSCs, leading to suppressed expression of collagen and α-smooth MCE公司 muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMCs were cocultured with IL-6−/− and retinaldehyde dehydrogenase 1−/− HSCs. Similar to murine data, human BMCs expressed

more IL-10 after coculturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion. Conclusion: Activated HSCs increase IL-10 expression in BMCs (CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis. (HEPATOLOGY 2012;56:1902–1912) For the past decade, clinical trials and experimental studies have suggested that infusion therapy of whole bone marrow cells (BMCs) has beneficial effects toward liver regeneration, injury, and fibrosis/cirrhosis by stimulating the proliferation of hepatocytes, increasing progenitor cells, and enhancing matrix degradation.1-3 However, the underlying mechanisms are unknown, in part because whole BMCs contain a wide range of cell types, including several types of stem and precursor cells of monocytic and granulocytic lineages.4 Events associated with hepatic fibrosis are well characterized, notably the excessive production of extracellular matrix (ECM) by activated hepatic stellate cells (HSCs).