Norepinephrine inhibits human immunodeficiency virus type-1 infection through the NF-kappaB inactivation.
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.
Moriuchi
Masako
M
Division of Medical Virology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
Yoshimine
Hiroyuki
H
Oishi
Kazunori
K
Moriuchi
Hiroyuki
H
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
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D009638:Norepinephrine