Morphine suppresses intracellular interferon-alpha expression in neuronal cells.
Interferon alpha (IFN-alpha) not only plays a key role in innate host immunity against infections but also is involved in the cellular functions of the central nervous system (CNS). In this study, we examined the impact of morphine on IFN-alpha expression in human neuronal cells (NT2-N). Similar to human immune cells, NT2-N cells also expressed IFN-alpha at both mRNA and protein levels. IFN-alpha expression in NT2-N cells, however, was inhibited by morphine. Naltrexone antagonized the inhibitory effect of morphine on IFN-alpha expression in NT2-N cells. The specific mu opioid receptor antagonist, Cys2, Tyr3, Arg5, Pen7-amide (CTAP), also blocked the morphine action on intracellular IFN-alpha expression. Investigation of the mechanisms involved in the morphine action showed that although morphine had little effect on the expression of key IFN regulatory factors (IRFs), morphine inhibited IFN-alpha promoter activation and suppressed the expression and phosphorylation of signal transducer and activator of transcription 1 (STAT1) in the neuronal cells. These findings provide direct in vitro evidence that opioids may impair neuronal cell-mediated innate protection in the CNS.
Wan
Qi
Q
Division of Allergy and Immunology, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, United States.
Wang
Xu
X
Wang
Yan-Jian
YJ
Song
Li
L
Wang
Shi-Hong
SH
Ho
Wen-Zhe
WZ
D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000187:drug effects; D014162:Transfection
D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D009271:Naltrexone; D009020:Morphine; D007371:Interferon-gamma