Toll‐like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia‐inducible factor 1α (HIF1A) and result in differential HIF1A‐dependent gene expression

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

关键词: dendritic cells;    poly I:C;    CpG;    LPS;    MYD88;    TRIF;    NOS2;    PTGS2;    HIF;   

DOI  :  10.1189/jlb.1210683

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HIF1Aisatranscriptionfactorthatplaysacentralrolefortheadaptationtotissuehypoxiaandfortheinflammatoryresponseofmyeloidcells,includingDCs.HIF1AisstabilizedbyhypoxiabutalsobyTLRligandsundernormoxicconditions.TheunderlyingsignalingeventsleadingtotheaccumulationofHIF1Ainthepresenceofoxygenarestillpoorlyunderstood.Here,weshowthatincontrasttohypoxicstabilizationofHIF1A,normoxic,TLR‐mediatedHIF1AaccumulationinDCsfollowsadifferentpathwaythatpredominantlyrequiresMYD88‐dependentNF‐κBactivity.TheTLR‐inducedHIF1Acontrolsasubsetofproinflammatorygenesthatareinsufficientlyinducedfollowinghypoxia‐mediatedHIF1Ainduction.Thus,TLRactivationandhypoxiastabilizeHIF1Aviadistinctsignalingpathways,resultingindifferentialHIF1A‐dependentgeneexpression...

【 授权许可】

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