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.
Li
Yuan
Y
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.
Ye
Li
L
Peng
Jin-Song
JS
Wang
Chuan-Qing
CQ
Luo
Guang-Xiang
GX
Zhang
Ting
T
Wan
Qi
Q
Ho
Wen-Zhe
WZ
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