ReferenceID 534

Cardiac glycosides are potent inhibitors of interferon-β gene expression

Nat Chem Biol

Here we report that bufalin and other cardiac glycoside inhibitors of the sodium-potassium ATPase (sodium pump) potently inhibit the induction of the interferon-β (IFNβ) gene by virus, double-stranded RNA or double-stran

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Reference Id
534
Evidence Id
17124
Core Evidence Id
17124
Source Reference Id
1034
Herb2 Reference Id
HBREF001760
Subject Paper Key
HBIN018981_21076398
Pubmed Id
21076398
Doi
10.1038/nchembio.476
Paper Title
Cardiac glycosides are potent inhibitors of interferon-β gene expression
Paper Abstract
Here we report that bufalin and other cardiac glycoside inhibitors of the sodium-potassium ATPase (sodium pump) potently inhibit the induction of the interferon-β (IFNβ) gene by virus, double-stranded RNA or double-stranded DNA. Cardiac glycosides increase the intracellular sodium concentration, which appears to inhibit the ATPase activity of the RNA sensor RIG-I, an essential and early component in the IFNβ activation pathway. This, in turn, prevents the activation of the critical transcription factors IRF3 and NFκB. Bufalin inhibition can be overcome by expressing a drug-resistant variant of the sodium pump and knocking down the pump by short hairpin RNA inhibits IFNβ expression. Thus, bufalin acts exclusively through the sodium pump. We also show that bufalin inhibits tumor necrosis factor (TNF) signaling, at least in part by interfering with the nuclear translocation of NFκB. These findings suggest that bufalin could be used to treat inflammatory and autoimmune diseases in which IFN or TNF are hyperactivated.
Journal
Nat Chem Biol
Publish Year
2011
Experiment Subject
Experiment Type
Others
Phenotype Related
Autoimmune Diseases
Paper Title Cn
Paper Title En
Cardiac glycosides are potent inhibitors of interferon-β gene expression
Bilingual Status
semi_complete