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

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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.