Morphine Negatively Regulates Interferon-γ Promoter Activity in Activated Murine T Cells through Two Distinct Cyclic AMP-dependent Pathways

摘要: To explore the mechanism by which morphine promotes incidence of HIV infection, we evaluated regulatory role on interferon-gamma (IFN-gamma) promoter in activated T cells from wild type and mu-opioid receptor knockout mice. Our results show that inhibited anti-CD3/CD28-stimulated IFN-gamma activity a dose-dependent manner. Chronic treatment increased intracellular cAMP. evaluate cAMP morphine's modulatory function, effects dibutyryl cyclic AMP forskolin were investigated. Both activity. Treatment with pertussis toxin, but not protein kinase A inhibitor, antagonized inhibitory effects. Morphine phosphorylation ERK1/2 p38 MAPK; addition, presence either or MAPK inhibitor (PD98059 SB203580) resulted an additive inhibition The transcription factor activator protein-1, NF-kappaB, nuclear (NFAT) negatively regulated morphine. Overexpression NF-kappaB p65 rescued effect However, only when NFATc1 was co-overexpressed c-fos counteracted. observed obtained mice, suggesting modulation is mediated through receptor. In summary, our data indicate two distinct cAMP-dependent pathways, signaling pathway ERK1/2, MAPK, AP-1/NFAT pathway.