Retinoic acid mimics transforming growth factor β in the regulation of human immunodeficiency virus expression in monocytic cells

Guido Poli, Audrey L. Kinter, Jesse S. Justement, Peter Bressler, John H. Kehrl, Anthony S. Fauci

Research output: Contribution to journalArticlepeer-review

Abstract

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 β (TGF-β). RA significantly inhibited phorbol ester-mediated, but not tumor necrosis factor α-mediated, induction of HIV transcription in the chronically infected promonocytic U1 cell line. RA and TGF-β also completely suppressed the induction of virus production in U1 cells by interleukin 6 alone or in combination with glucocorticoids, which predominantly up-regulate virus expression at the posttranscriptional level. Despite the close parallel to TGF-β-induced effects, no evidence was obtained that RA mediated its effect by inducing secretion of active TGF-β1, -β2, or -β3. 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-β. In contrast, stimulation of monocyte-derived macrophages or U937 cells (the parental cell line of U1) with either RA or TGF-β 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.

Original languageEnglish
Pages (from-to)2689-2693
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number7
Publication statusPublished - 1992

Keywords

  • Cytokines
  • Macrophage
  • Phorbol 12-myristate 13-acetate
  • U1 cells
  • U937 cells

ASJC Scopus subject areas

  • Genetics
  • General

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