Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

Abstract

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…112,[115][116][117] It has been proposed that overexpression of TGF-b can result in alteration of its functions from protective to pathogenic ones. SP contains large amounts of prostaglandins of the E series (PGE) Prostaglandins are potent immunomediators involved in numerous physiological and pathogenetic processes.…”

Recombinant interleukin 4 stimulates human immunodeficiency virus production by infected monocytes and macrophages

“…Several cytokines have been reported to influence production of HIV by infected monocytes or monocytoid cell lines, during either initial or chronic infection. Hence, interleukins (ILs) 1, 2, 3 and 6, tumour necrosis factor (TNF)-c~, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) have been reported to augment HIV production by infected monocytes (Koyanagi et al, 1988;Folks et al, 1989;Matsuyama et al, 1989;Nakajima et al, 1989;Poli et al, 1990), whereas interferons (IFNs) y, o~ and fl, and transforming growth factor (TGF) fl have been reported to decrease production (Kornbluth et aL, 1990;Poli et al, 1991). Conversely, HIV infection of monocytes has been reported to stimulate production of cytokines such as IL-1, IL-6 and TNF-~ (Poli et al, 1989;Nakajima et al, 1989).…”

Cell-Type-Dependent Effect of Transforming Growth Factor β, a Major Cytokine in Breast Milk, on Human Immunodeficiency Virus Type 1 Infection of Mammary Epithelial MCF-7 Cells or Macrophages

“…Colostrum contains 140 pg (67 to 186 pg) of TGF-␤1 and 3,325 pg (1,376 to 5,394 pg) of TGF-␤2 per ml, while mature milk contains 83 pg (17 to 114 pg) of TGF-␤1 and 1,644 pg (592 to 2,697 pg) of TGF-␤2 per ml (9). TGF-␤ acts as an anti-HIV-1 or pro-HIV-1 factor, depending on cell type, virus strain, timing of treatment, or combination of other factors (13,15,17,27); however, no substantial differences in effects on HIV infection among the TGF-␤ isoforms could be found (13). Here we studied whether TGF-␤ influences HIV-1 expression in major breast milk cells such as mammary epithelial cells and macrophages.…”