TY - JOUR
T1 - 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
AU - Chen, Qiuyan
AU - Ma, Yifan
AU - Ross, A. Catharine
PY - 2002
Y1 - 2002
N2 - 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-α (TNF-α), interferon-β (IFN-β), and IFN-γ, 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-β or IFN-γ. However, in contrast, RA reduced STAT-1 activation and gene expression induced by LPS and/or TNF-α by about 50-70%, and lowered in vitro DNA binding activity to both a STAT-1 consensus element and a nuclear factor kappa B (NFκB) 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 NFκB pathway.
AB - 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-α (TNF-α), interferon-β (IFN-β), and IFN-γ, 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-β or IFN-γ. However, in contrast, RA reduced STAT-1 activation and gene expression induced by LPS and/or TNF-α by about 50-70%, and lowered in vitro DNA binding activity to both a STAT-1 consensus element and a nuclear factor kappa B (NFκB) 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 NFκB pathway.
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U2 - 10.1046/j.1365-2567.2002.01485.x
DO - 10.1046/j.1365-2567.2002.01485.x
M3 - Article
C2 - 12383199
AN - SCOPUS:0036411908
SN - 0019-2805
VL - 107
SP - 199
EP - 208
JO - Immunology
JF - Immunology
IS - 2
ER -