Findings in antivirals reported from Nagasaki University

   "Tacrolimus (Tac), but not cyclosporin A (CyA), had an inhibitory effect on IFN-a-induced double-stranded ribonucleic acid (RNA)-dependent protein kinase (PKR) in a dose-dependent manner. STAT-1 also acted in a similar fashion to PKR. IFN-alpha combined with Tac attenuated the ISRE-containing promoter gene activity as compared with IFN-a alone. In contrast, its expression in pretreated CyA was slightly attenuated. In pretreated Tac, but not CyA, the levels of IFN-a-induced tyrosine phosphorylated STAT-1 and -2 were clearly lower than those induced by IFN-a alone. Tac and CyA did not decrease the IFN-a-induced JAK-1 phosphorylation. The nuclear translocation rate of tyrosine phosphorylated STAT-1 was inhibited by pretreatment of both Tac and CyA by western blotting and immunohistochemistry. In an HCV replicon system, pretreated Tac diminished the replication inhibitory effect of IFN-a. In this study, we show that calcineurin inhibitors, especially Tac, are the negative regulators of IFN signaling in the hepatocyte; the greatest cause of such inhibition is the phosphorylation disturbance of STAT-1, next to inhibition of the nuclear translocation of STAT-1," wrote K. Hirano and colleagues, Nagasaki University.

   The researchers concluded: "Disturbance of tyrosine phosphoryiation of STAT-1 resulted in diminished ISRE-containing promoter activity and a decline in antiviral protein expression. Moreover, the replication of HCV was activated. This phenomenon is detrimental to IFN therapy after liver transplantation, and the selection of calcineurin inhibitors may warrant further discussion depending on the transplant situation."

   Hirano and colleagues published the results of their research in Liver Transplantation (Differential effects of calcineurin inhibitors, tacrolimus and cyclosporin A, on interferon-induced antiviral protein in human hepatocyte cells. Liver Transplantation, 2008;14(3):292-298).

   For additional information, contact T. Ichikawa, Nagasaki University, Graduate School Biomedical Science, Dept. of Internal Medicine 1, 1-7-1 Sakamoto, Nagasaki 8528501, Japan.

   The publisher of the journal Liver Transplantation can be contacted at: John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

   Keywords: Japan, Sakamoto, Antivirals, Antiviral, Bioengineering, Biomedical Engineering, Biomedicine, Cyclosporin A, Drugs, Enzyme Research, Gastroenterology, HCV, Hepatitis C Virus, Hepatology, Infectious Disease, Interferon, Kinase, Liver Transplant, Organ Transplant, Pharmaceuticals, Tacrolimus, Transplantation, Treatment, Viral Inhibition, Viral Therapy, Virology, Nagasaki University.

   This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2008, Biotech Business Week via NewsRx.com.

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