The mononuclear cells were analyzed by FACS using macrophages marker (CD11b, CD11c, CD206, Gr-1, F4/80, Ly6C) and the cytokines http://www.selleckchem.com/products/AG-014699.html production (TNFa, IL-6, arginase). Further, we compared with tissue macrophages number and cytokine production in the same tissue following rVVN25 treatment. To confirm the effect of tissue macrophages in liver disease of HCV Tg mice, we were injected intravenously with clodronate liposomes and examined serum ALT activity,

HCV core protein level, cell number and observed histological features. Finally, we analyzed liver disease and the function and number in tissue macrophages with Tg mice following neutralizing anti-IL-6R antibody. Results: The number of CD11b+F4/80+macrophages in this website the liver and spleen but not SVF was increased under HCV expressed condition

and especially CD11b+F4/80+CD11c-CD206+M2 macrophages remarkably increased. In addition, these M2 as well as M1 macrophages were produced TNF-a and IL-6 much higher with HCV Tg mice. rVV-N25 treatment suppressed cell number and cytokine production on macrophages in the liver and spleen. However, TNF-a production from M2 macrophages was increased in the SVF. We also showed that pathological findings in the liver have improved by depletion of macrophage even though HCV core level was not suppressed. Finally, aIL-6R antibody treatment reduced the number of macrophages and induced normal pathological findings. Conclusions: M2 macrophages contribute to the induction of chronic liver inflammation in HCV mouse models. In addition, rVV-N25 treatment induced therapeutic effect on liver tissue due to suppressed macrophage recruitment and activation. Disclosures: The following people have nothing to disclose: Kiminori Kimura, MCE公司 Takahiro Ohtsuki, Yuko Tokunaga, Michinori Kohara Liver fibrosis progression and regression are modulated by cells of the innate immune system, especially macrophages. Macrophages can be roughly classified as classically activated

and alternatively activated (M1 and M2, respectively). While M2 have been implicated in fibrogenesis, the overall functional role of M1 and M2 in liver fibrosis remains largely unknown. M2 polarization is controlled by signaling transmitted through IL-4 and IL-13 ligation to receptors IL-4Ra1 (and IL-13Ra1). This correlates with upregulation of M2-related genes such as Stat6, Arg1, YM1 and Mrc1. We therefore aimed to define the role of IL-4Ra1 as central receptor for M2 polarization in liver fibrosis progression and spontaneous recovery. We used the mouse models of CCl4-induced (6 weeks by oral gavage) and spontaneous biliary liver fibrosis (Mdr2 KO). In the CCL4 model, IL4Ra1 expression was increased >2-fold after 6 weeks and reduced 1.5-fold 2 weeks after the last dose. In Mdr2 KO mice, IL-4Ra1 expression gradually increased until age 6-wk, and decreased thereafter.