Cholesterol 25‐hydroxylase production by dendritic cells and macrophages is regulated by type I interferons

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: innate immunity;    lung;    STAT1;    TLR;    LPS;    poly I:C;   

DOI  :  10.1189/jlb.0610318

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theoxysterol‐producingenzymeCH25Hplaysanimportantroleinregulatinglipidmetabolism,geneexpression,andimmuneactivation.InvitroexperimentsusingapanelofTLRagoniststoactivateBMDCsandmacrophagesdemonstratedthatCh25hexpressionisinducedrapidly,selectively,androbustlybytheTLRligandspolyI:CandLPS.ThemechanismofTLR3‐andTLR4‐inducedtranscriptionlevelsofCh25hreliesontheTRIF‐mediatedproductionoftypeIIFNsandrequiressignalingthroughtheIFNαRandJAK/STAT1pathway.TreatmentofBMDCsandmacrophageswithIFN‐αorIFN‐βinducesCh25hinaSTAT1‐dependentmanner.IFN‐γalsoup‐regulatedCh25hexpressionbysignalingthroughSTAT1,suggestingthatmultiplepathwaysregulatetheproductionofthisenzyme.Inaddition,wedemonstratedthatregulationofCh25hexpressioninvivoinlung‐derivedDCsandmacrophagesisdependentonsignalingthroughtheIFNαRandSTAT1.TheresultssuggestthattherapidinductionofCh25handsubsequentoxysterolsynthesismayrepresentacomponentoftheregulatorynetworkthatmodulatesthemagnitudeofinnateimmunereactionsandpossiblythenatureandintensityofsubsequentadaptiveresponses...

【 授权许可】

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