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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
Author(s) -
Chen Qiuyan,
Ma Yifan,
Ross A. Catharine
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01485.x
Subject(s) - stat protein , stat , stat4 , retinoic acid , microbiology and biotechnology , jak stat signaling pathway , stat3 , cytokine , biology , activator (genetics) , stat1 , tyrosine phosphorylation , tumor necrosis factor alpha , transcription factor , signal transduction , cancer research , immunology , tyrosine kinase , receptor , biochemistry , gene
Summary 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.