Glycyrrhizin and isoliquiritigenin suppress the LPS sensor Toll‐like receptor 4/MD‐2 complex signaling in a different manner

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

关键词: innate immunity;    Glycyrrhiza uralensis;    NF‐;    κ;    B;    MAPK;    IL‐;    6;   

DOI  :  10.1189/jlb.0112038

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Recentevidencessuggestthattheextractsofplantproductsareabletomodulateinnateimmuneresponses.AsaponinGLandachalconeILGarerepresentativecomponentsofGlycyrrhizauralensis,whichattenuateinflammatoryresponsesmediatedbyTLRs.Here,weshowthatGLandILGsuppressdifferentstepsoftheLPSsensorTLR4/MD‐2complexsignalingatthereceptorlevel.ExtractofG.uralensissuppressedIL‐6andTNF‐αproductioninducedbylipidAmoietyofLPSinRAW264.7cells.AmongvariousG.uralensis‐relatedcomponentsofsaponinsandflavanones/chalcones,GLandILGcouldsuppressIL‐6productioninducedbylipidAindose‐dependentmannersinRAW264.7cells.Furthermore,elevationofplasmaTNF‐αinLPS‐injectedmicewasattenuatedbypassiveadministrationofGLorILG.GLandILGinhibitedlipidA‐inducedNF‐κBactivationinBa/F3cellsexpressingTLR4/MD‐2andCD14andBMMs.ThesecomponentsalsoinhibitedactivationofMAPKs,includingJNK,p38,andERKinBMMs.Inaddition,GLandILGinhibitedNF‐κBactivationandIL‐6productioninducedbypaclitaxel,anonbacterialTLR4ligand.Interestingly,GLattenuatedtheformationoftheLPS‐TLR4/MD‐2complexes,resultingininhibitionofhomodimerizationofTLR4.AlthoughILGdidnotaffectLPSbindingtoTLR4/MD‐2,itcouldinhibitLPS‐inducedTLR4homodimerization.TheseresultsimplythatGLandILGmodulatetheTLR4/MD‐2complexatthereceptorlevel,leadingtosuppressLPS‐inducedactivationofsignalingcascadesandcytokineproduction,buttheireffectsareexertedatdifferentstepsofTLR4/MD‐2signaling...

【 授权许可】

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