Retinoic acid mimics transforming growth factor beta in the regulation of human immunodeficiency virus expression in monocytic cells.
Retinoic acid (RA) exerts potent suppressive and upregulatory effects on human immunodeficiency virus (HIV) expression in mononuclear phagocytes, strikingly similar to the effects of the cytokine transforming growth factor beta (TGF-beta). RA significantly inhibited phorbol ester-mediated, but not tumor necrosis factor alpha-mediated, induction of HIV transcription in the chronically infected promonocytic U1 cell line. RA and TGF-beta also completely suppressed the induction of virus production in U1 cells by interleukin 6 alone or in combination with glucocorticoids, which predominantly upregulate virus expression at the posttranscriptional level. Despite the close parallel to TGF-beta-induced effects, no evidence was obtained that RA mediated its effect by inducing secretion of active TGF-beta 1, -beta 2, or -beta 3. As with chronically infected U1 cells, similar inhibitory effects were also observed in primary monocyte-derived macrophages previously infected with HIV and then exposed to either RA or TGF-beta. In contrast, stimulation of monocyte-derived macrophages or U937 cells (the parental cell line of U1) with either RA or TGF-beta prior to in vitro infection resulted in the enhancement of virus production. Given the already successful use of retinoids in the treatment of several malignancies and the present demonstration of their capability of blocking the induction of HIV expression in infected mononuclear phagocytes, it would be of interest to pursue the potential role of this class of compounds in the development of strategies aimed at the pharmacologic regulation of HIV expression.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
G
G
Poli
A L
AL
Kinter
J S
JS
Justement
P
P
Bressler
J H
JH
Kehrl
A S
AS
Fauci
D006678:HIV / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000382:microbiology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D016212:Transforming Growth Factor beta; D014212:Tretinoin; D012194:RNA-Directed DNA Polymerase; D013755:Tetradecanoylphorbol Acetate