Glucocorticoids synergize with tumor necrosis factor alpha in the induction of HIV expression from a chronically infected promonocytic cell line.
In this study we have investigated the effects of glucocorticoids (GCs) on the expression of human immunodeficiency virus (HIV) in a chronically infected promonocytic cell line, U1. Although no increase in virus production was observed in U1 cells stimulated with physiological concentrations of GC alone, costimulation with dexamethasone plus tumor necrosis factor alpha (TNF-alpha) synergistically enhanced TNF-alpha-dependent HIV expression. Molecular analysis demonstrated that GCs plus TNF-alpha resulted in an accumulation of steady state HIV RNA secondary to either an increase in transcription or an increase in message stability. These findings may be of physiological relevance because GCs are used in the treatment of certain disorders associated with HIV infection and TNF-alpha levels have been reported to be elevated in the plasma and cerebrospinal fluid of certain HIV-infected individuals.
Bressler
P
P
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Poli
G
G
Justement
J S
JS
Biswas
P
P
Fauci
A S
AS
D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006678:HIV / Q000187:drug effects / Q000254:growth & development*; D015488:HIV Antigens / Q000096:biosynthesis; D009000:Monocytes / Q000382:microbiology; D012333:RNA, Messenger / Q000096:biosynthesis; D013234:Stem Cells / Q000382:microbiology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D015488:HIV Antigens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone