Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.. and Mann-Whitney value is shown in panel B. The Ki67+ bile duct cells Mitragynine were also compared in liver samples. As shown in Fig. 2, Ki67+ bile duct cells were detected more frequently in all cirrhotic livers compared to normal healthy controls. HCV cirrhotic livers had the highest percentage of Ki67+ bile duct cells compared to alcoholic cirrhosis or alcoholic plus HCV cirrhosis. Open in a separate window Fig. 2 Ki67 staining in bile duct cells in cirrhotic livers. (A) Panel A shows the representative positive immunostaining with Ki67 antibody in bile duct cells in normal healthy livers (normal) and cirrhotic livers. (B) Panel B summarizes the percentage of Ki67+ bile duct cells. Values are shown as means SEM from 13 to 20 patients. The value is shown in panel B. N.S: not significant. Activation of STAT3 in human cirrhotic livers: suppression in alcoholic cirrhosis The above data suggest that liver regeneration is suppressed in alcoholic cirrhosis. To understand the underlying mechanisms, we compared STAT3 activation in these cirrhotic liver samples by immunohistochemistry analysis of phospho-STAT3 (p-STAT3). As shown in Fig. 3A, pSTAT3 positive staining was rarely detected in normal healthy livers. In contrast, significant pSTAT3 positive staining was observed in all cirrhotic livers with staining in hepatocytes, bile duct cells, nonparenchymal cells, and inflammatory cells. pSTAT3+ hepatocytes were observed frequently around the inflammatory region. Fig. 3B shows that the percentage of pSTAT3+ hepatocytes in all 3 forms of cirrhosis was significantly higher than in normal healthy livers. Compared to HCV cirrhotic livers, alcoholic cirrhotic or alcoholic plus HCV cirrhotic livers had significantly lower percentage of pSTAT3+ hepatocytes. Open in a separate window Fig. 3 pSTAT3 staining in hepatocytes of end-stage liver cirrhosis. (A) Panel A shows the representative positive immunostaining with anti-phopho-STAT3 antibody in hepatocytes in normal healthy livers (normal) and cirrhotic livers. Arrows indicate pSTAT3+ hepatocytes. (B) Panel B summarizes the percentage of pSTAT3+ hepatocytes. Values are shown as means SEM from 13 to 20 patients. The value is shown in panel B. N.S: not Mitragynine significant. We also examined the STAT3 phosphorylation in bile duct cells in liver samples. As shown in Fig. 4A, pSTAT3 was rarely detected in bile duct cells of normal healthy livers, whereas significant pSTAT3 staining was detected in the bile duct cells of HCV, alcoholic and HCV+alcoholic cirrhotic liver tissues. The pSTAT3 in bile duct like cells was also confirmed by double staining with anti-pSTAT3 and anti-CK19 antibodies. As shown in Fig. 4B, the left panel shows representative bile duct cells with pSTAT3 negative staining (CK19+pSTAT3?), Mitragynine and the right panel shows the representative bile duct like cells with pSTAT3 positive staining Mitragynine (CK19+pSTAT3+). The percentage of pSTAT3+ duct cells in all 3 forms of cirrhosis was significantly higher than in normal SLI healthy livers, and that HCV cirrhotic livers had more pSTAT3+ bile duct cells than alcoholic cirrhosis and alcoholic plus HCV cirrhosis (Fig. 4C). Open in a separate window Fig. 4 Phosphorylation of STAT3 in bile duct like cells of end-stage liver cirrhosis. Panel A shows the representative immunostaining with anti-phopho-STAT3 antibody in normal healthy livers and end-stage human cirrhotic livers. Panel B shows the representative double immunostaining with anti-pSTAT3 and anti-CK19 antibodies. pSTAT3+ bile duct cells were stained in nuclei (brown), while CK19+ , a marker for bile duct cells, were stained in cytoplasm (nickel). Panel C summarizes the percentage of pSTAT3+ bile duct like cells. Values are shown as means SEM from 13 to 20 patients. The value is shown in panel C. N.S: not significant. A positive correlation between pSTAT3+ and Ki67+ hepatocytes or Ki67+ bile duct cells The hepatoprotective function of STAT3 has been well documented (Gao, 2005), and STAT3 mRNA has been shown to correlate inversely with serum levels of alanine transaminase (Larrea et al., 2006). Next, we asked whether pSTAT3 in these samples had any correlation with liver injury (serum levels of.