Opposing cytokine-specific effects of all trans-retinoic acid on the activation and expression of signal transducer and activator of transcription (STAT)-1 in THP-1 cells.
The regulation of signal transducer and activator of transcription-1 (STAT-1) by cytokines and all-trans-retinoic acid (RA) was investigated in THP-1 monocytic cells cultured with RA and stimulated with lipopolysaccharide (LPS), tumour necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), and IFN-gamma, individually or in combinations. While RA (10(-8) m) alone did not alter STAT-1 activation or expression in THP-1 cells, RA enhanced or prolonged STAT-1 activation (tyrosine 701 phosphorylation) and gene expression (mRNA and protein) induced by either IFN-beta or IFN-gamma. However, in contrast, RA reduced STAT-1 activation and gene expression induced by LPS and/or TNF-alpha by about 50-70%, and lowered in vitro DNA binding activity to both a STAT-1 consensus element and a nuclear factor kappa B (NFkappaB) binding element. These results imply that RA can significantly rebalance STAT-1-dependent responses, and that one of the mechanisms may be through the inhibition of the NFkappaB pathway.
Chen
Qiuyan
Q
Department of Nutritional Sciences, The Pennsylvania State University, 126-S Henderson Building, University Park, PA 16802, USA.
Ma
Yifan
Y
Ross
A Catharine
AC
D016207:Cytokines / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D015534:Trans-Activators / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin