title: Norepinephrine inhibits human immunodeficiency virus type-1 infection through the NF-kappaB inactivation.
abstract: Exercise or acute stress can exert significant effects on immune system as well as cardiovascular and respiratory systems through catecholamines. In this study, we investigated effects of norepinephrine (NE), a catecholamine neurotransmitter on human immunodeficiency virus type-1 (HIV-1) infection. NE inhibited in vitro HIV-1 infection of peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo HIV-1 replication in patients' PBMC. In transient expression assays, NE downregulated HIV-1 long terminal repeat, but site-directed mutagenesis on NF-kappaB-binding sites or cotreatment with H89 (a protein kinase A inhibitor) abrogated the NE-mediated effect. Gel-shift assays showed suppression of NF-kappaB activity in NE-treated cells. NE increased cytoplasmic levels of IkappaB-alpha, a natural inhibitor of NF-kappaB. Thus, NE apparently inhibits HIV-1 infection, at least in part through NF-kappaB inactivation.
authors.affiliation: Division of Medical Virology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Moriuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshimine
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriuchi
mesh_terms: D000328:Adult; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding
chemical_list: D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009638:Norepinephrine