N-acetyl-L-cysteine-induced up-regulation of HIV-1 gene expression in monocyte-derived macrophages correlates with increased NF-kappaB DNA binding activity

• Published in: Journal of leukocyte biology Vol. 61; no. 1; pp. 33 - 39
• Main Authors: Nottet, H S, Moelans, I I, de Vos, N M, de Graaf, L, Visser, M R, Verhoef, J
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-01-1997
• Subjects: Acetylcysteine - pharmacology; AIDS/HIV; Anti-HIV Agents - pharmacology; Cells, Cultured; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - metabolism; DNA, Viral - metabolism; Genes, Reporter - drug effects; Genetic Vectors; HIV Long Terminal Repeat - drug effects; HIV Long Terminal Repeat - genetics; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Humans; Jurkat Cells; Macrophages - drug effects; Macrophages - metabolism; Macrophages - virology; NF-kappa B - metabolism; Transcription, Genetic - drug effects; Transfection; Up-Regulation - drug effects; Virus Replication - drug effects
• ISSN: 0741-5400; 1938-3673

Nuclear factor kappaB (NF-kappaB) is an important cellular regulator of human immunodeficiency virus (HIV) gene expression. In T cells, N-acetyl-L-cysteine (NAC) inhibits the induction of NF-kappaB and transcription of HIV-1. However, NAC up-regulates HIV-1 replication in monocyte-derived macrophages (MDM). In this study we demonstrate that NAC treatment of MDM transfected with a chloramphenicol acetyltransferase (CAT) construct under transcriptional control of the HIV-1 long terminal repeat resulted in an up-regulation of CAT activity. Furthermore, MDM transfected with a HIV-1-NF-kappaB-CAT construct also produced increased CAT activity after NAC treatment. In addition, electrophoretic mobility shift assays revealed that nuclei of NAC-treated MDM contained increased binding activity to wild-type, but not mutant, kappaB oligonucleotides. Components of the binding activity were identified with antibodies as the NF-kappaB subunits p50 and p65. These data indicate that NAC-induced enhancement of HIV-1 replication in MDM is regulated at the level of viral gene expression and mediated by NF-kappaB.