Cell-type-dependent effect of transforming growth factor beta, a major cytokine in breast milk, on human immunodeficiency virus type 1 infection of mammary epithelial MCF-7 cells or macrophages.
Breastfeeding plays a substantial role in mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). Mammary epithelial cells, as well as macrophages and lymphocytes, are thought to serve as sources of the virus in breast milk. Soluble factors in breast milk exert various biological functions, including immune tolerance or immune modulation, and may influence milk-borne infection with HIV-1. In this study we show that transforming growth factor beta (TGF-beta), a major cytokine in breast milk, inhibited HIV-1 infection of mammary epithelial MCF-7 cells but enhanced that of macrophages. TGF-beta downregulated the HIV-1 long terminal repeat (LTR) promoter in MCF-7 cells but upregulated it in macrophages. Stimulation with TGF-beta suppressed NF-kappaB binding to the HIV-1 LTR in MCF-7 cells, at least in part by downregulating induced IkappaB kinase expression. Cell type-dependent effects of TGF-beta on HIV-1 expression may play a role in milk-borne infection with HIV-1.
Moriuchi
Masako
M
Department of Pediatrics, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Moriuchi
Hiroyuki
H
D001665:Binding Sites; D001943:Breast Neoplasms / Q000821:virology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology; D051858:Forkhead Transcription Factors; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase; D008264:Macrophages / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D004268:DNA-Binding Proteins; C510350:FOXH1 protein, human; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D016328:NF-kappa B; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human