Abstract
Chronic morphine treatment in animal models has been shown to alter a number of immune parameters including suppression of cellular immunity. T helper cell differentiation into Th2 effector cell may be a major contributing factor to impaired cellular immunity following chronic drug abuse. We had previously shown that chronic morphine treatment in vivo and in vitro decreases IL-2 and IFNgamma (Th1) protein levels and increases IL-4 and IL-5 (Th2) protein levels in a time-dependent manner. In addition in this paper, we show that chronic morphine treatment resulted in a decrease in IFNgamma and IL-2 mRNA and an increase in IL-4 and IL-5 mRNA accumulation in murine splenocytes. Furthermore, chronic morphine treatment inhibited IFNgamma promoter activity and increased IL-4 promoter activity in respective promoter transfected primary T cells. In addition, we also demonstrate that chronic morphine treatment resulted in an increase in GATA 3 binding to DNA consensus elements in electromobility shift assays and an increase in GATA 3 protein and mRNA levels. In contrast, chronic morphine treatment resulted in a decrease in T-bet mRNA levels. From these data, we conclude that chronic morphine treatment differentiates T helper cell to Th2 effector cells by modulating key master switches that results in committing T helper cell to a Th2 phenotype.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies / pharmacology
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Blotting, Western / methods
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CD28 Antigens / immunology
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CD3 Complex / immunology
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Cell Count / methods
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Cell Differentiation / drug effects
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Cells, Cultured
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Cytokines / genetics
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Cytokines / metabolism
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dose-Response Relationship, Drug
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Electrophoretic Mobility Shift Assay / methods
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GATA3 Transcription Factor
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Mice
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Mice, Knockout
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Morphine / pharmacology*
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Narcotics / pharmacology*
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / physiology
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Protein Binding
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RNA, Messenger / biosynthesis
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RNA, Messenger / drug effects
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Reverse Transcriptase Polymerase Chain Reaction / methods
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T-Box Domain Proteins
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T-Lymphocytes, Helper-Inducer / drug effects*
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T-Lymphocytes, Helper-Inducer / metabolism
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Th1 Cells / drug effects
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Th1 Cells / metabolism
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Th2 Cells / drug effects*
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Th2 Cells / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Antibodies
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CD28 Antigens
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CD3 Complex
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Cytokines
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Narcotics
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RNA, Messenger
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Trans-Activators
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Transcription Factors
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Morphine
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DNA