Morphine inhibits intrahepatic interferon- alpha expression and enhances complete hepatitis C virus replication.
Heroin addicts are a high-risk group for hepatitis C virus (HCV) infection and the development of chronic HCV disease. We thus examined whether morphine, the active metabolite of heroin, has the ability to inhibit intrahepatic interferon (IFN)- alpha expression, facilitating HCV replication in human hepatocytes. Morphine inhibited intrahepatic IFN- alpha expression, which was associated with an increase in HCV replication in hepatocytes. Moreover, morphine compromised the anti-HCV effect of recombinant IFN- alpha . Investigation of the mechanism responsible for the morphine action revealed that morphine inhibited expression of IFN regulatory factor 5 in the hepatocytes. In addition, morphine suppressed the expression of p38, an important signal-transducing molecule involved in IFN- alpha -mediated anti-HCV activity. These findings indicate that morphine plays a cofactor role in facilitating HCV persistence in human hepatocytes.
Division of Allergy and Immunology, Joseph Stokes, Jr., Research Institute, Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Yuan
Y
Li
Li
L
Ye
Jin-Song
JS
Peng
Chuan-Qing
CQ
Wang
Guang-Xiang
GX
Luo
Ting
T
Zhang
Qi
Q
Wan
Wen-Zhe
WZ
Ho
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D016898:Interferon-alpha / Q000096:biosynthesis*; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine