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Inflammation. 25-Hydroxycholesterol Suppresses interleukin-1-driven Inflammation Downstream of Type I Interferon

Inflammation. 25-Hydroxycholesterol Suppresses interleukin-1-driven Inflammation Downstream of Type I Interferon

Andrea Reboldi, Eric V Dang, Jeffrey G McDonald, Guosheng Liang, David W Russell, Jason G Cyster

Science. 2014 Aug 8;345(6197):679-84.

PMID: 25104388

Abstract:

Type I interferon (IFN) protects against viruses, yet it also has a poorly understood suppressive influence on inflammation. Here, we report that activated mouse macrophages lacking the IFN-stimulated gene cholesterol 25-hydroxylase (Ch25h) and that are unable to produce the oxysterol 25-hydroxycholesterol (25-HC) overproduce inflammatory interleukin-1 (IL-1) family cytokines. 25-HC acts by antagonizing sterol response element-binding protein (SREBP) processing to reduce Il1b transcription and to broadly repress IL-1-activating inflammasomes. In accord with these dual actions of 25-HC, Ch25h-deficient mice exhibit increased sensitivity to septic shock, exacerbated experimental autoimmune encephalomyelitis, and a stronger ability to repress bacterial growth. These findings identify an oxysterol, 25-HC, as a critical mediator in the negative-feedback pathway of IFN signaling on IL-1 family cytokine production and inflammasome activity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2140467	25-Hydroxycholesterol		2140-46-7	Price

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