Expression of CXC chemokines lacking ELR-motif in liver diseases and its clinical significance

人类研究：慢性肝病患者血清干扰素诱导蛋白10(IP-10)水平升高，与血清AST和ALT评估的肝脏炎症成比例，与病因无关。血清IP-10水平与肝炎的组织学活动也有很好的相关性。无论在病毒性肝炎还是自身免疫性肝炎中，IP-10mRNA的表达均见于肝小叶内的肝细胞内，肝小叶周围有淋巴细胞的浸润性。我们不能建立稳定的人Mig的ELISA体系，也不能确认人肝组织中Mig的阳性信号。我们还检测了肝细胞癌患者的血清IP-10水平。虽然肝癌患者血清IP-10水平升高，但IP-10水平与肿瘤大小及血清肿瘤标志物水平均无明显相关性。失代偿期肝细胞癌患者或肝组织炎症活动度较高的肝细胞癌患者血清IP-10水平往往较高。动物研究：我们建立了小鼠IP-10和Mig两种趋化因子的酶联免疫吸附试验系统，可以评价这两种趋化因子的水平。在未处理的对照小鼠中，趋化因子低于检测下限。在小鼠实验性肝损伤模型中，血清中这些趋化因子的水平随着肝损伤的进展而升高，以血清AST和ALT的水平来评估。Northern印迹法检测到IP-10和Mig的mRNA在肝脏炎症发生之前就在肝脏中检测到。原位杂交结果显示，肝细胞和肝窦细胞均表达这两种趋化因子的mRNA。

Human Studies:The serum levels of interferon inducible protein 10 (IP-10) were elevated in patients with chronic liver diseases in proportion to the hepatic inflammation as assessed by serum AST and ALT, irrespective of the etiology. The serum levels of IP-10 also correlated well with the histological activity of hepatitis. The mRNA expression of IP-10 was observed in the hepatocytes in hepatic lobules which were surrounded by infiltrating lymphocytes not only in viral hepatitis but also in autoimmune hepatitis. We could not make a stable ELISA system for human Mig and we could not confirm the positive signal of Mig in human liver tissues.We also measured the serum levels of IP-10 in patients with hepatocellular carcinoma (HCC). Although the serum levels of IP-10 in HCC were increased in HCC patients, the levels of IP-10 did not show a significant correlation with the tumor sizes nor the levels of serum tumor markers. The decompensated HCC patients or HCC patients with higher hepatic inflammatory activity tended to show higher levels of serum IP-10.Animal Studies:We made a ELISA systems of murine IP-10 and Mig which can evaluate the levels of these two chemokines. In control untreated mice, the chemokines were lower than the limits of detection. In experimental models of mouse liver injury, the serum levels of these chemokines increased as the progress of liver injury as assesses by the serum levels of AST and ALT.By Northern blotting study, the mRNA of IP-10 and Mig was detected in the liver preceding the onset of hepatic inflammation. The in situ hybridization revealed that both hepatocytes and hepatic sinusoidal cells expressed the mRNA of these two chemokines.