Reduction of indoxyl sulfate by AST‐120 attenuates monocyte inflammation related to chronic kidney disease

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

关键词: uremic toxin;    atherosclerosis;    leukocyte–;    endothelial interactions;    adhesion molecule;    oxidative stress;   

DOI  :  10.1189/jlb.0112023

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AcceleratedcardiovasculardiseaseisafrequentcomplicationofCKD.Monocyte‐mediatedinflammationandadhesionofmonocytestovascularendotheliumarekeyeventsinatherogenesis.Anoraladsorbent,AST‐120,retardsrenalfunctiondeteriorationbyloweringIS,whichisknowntoaccumulateinCKDpatients.However,theeffectofAST‐120onCKD‐relatedmonocyteactivationisunknown.WeaimedtodeterminewhetherAST‐120improvesmonocyte‐mediatedinflammationthroughISreduction.FlowcytometricanalysisshowedthatMac‐1expressionandROSproductionweresignificantlyhigherinperipheralbloodmonocytesofsubtotalNxCKDmicethaninsham‐operatedmice.AST‐120treatmentsignificantlydecreasedMac‐1expressionandROSproductioninCKDmodelmice.Furthermore,administrationofISinducedmonocyte‐mediatedinflammationandROSgeneration.InvitrostudiesindicatedthatISdose‐dependentlyincreasedTHP‐1monocyticcelladhesiontoIL‐1β‐activatedHUVECsunderphysiologicalflowconditions.ISalsoinducedmonocyte‐mediatedinflammationandROSproductioninTHP‐1cells.Phosphorylationofp38MAPKandmembranetranslocationofNAD(P)Hoxidasesubunitp47phoxinTHP‐1cellswereinducedbyIS.BothSB203580(p38MAPKinhibitor)andapocynin[NAD(P)Hoxidaseinhibitor]reducedTHP‐1celladhesiontoHUVECs.ApocyninalsoinhibitedIS‐inducedROSproductioninTHP‐1cells.ISinducedmonocyte‐driveninflammationthroughNAD(P)Hoxidase‐andp38MAPK‐dependentpathwaysinmonocytes.ThemainfindingofthisstudywasthatAST‐120inhibitedmonocyteactivationbyreducingISinvivo.ThisprovidesnewinsightsonhowAST‐120attenuatestheprogressionofatherosclerosisinCKD...

【 授权许可】

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