Molecular Mechanisms Responsible for the ReducedExpression of Cholesterol Transporters From Macrophagesby Low-Dose Endotoxin还原作用的分子机制 巨噬细胞胆固醇转运体的表达 Low Dose Endotoxin

《Molecular Mechanisms Responsible for the ReducedExpression of Cholesterol Transporters From Macrophagesby Low-Dose Endotoxin还原作用的分子机制 巨噬细胞胆固醇转运体的表达 Low Dose Endotoxin》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、MolecularMechanismsResponsiblefortheReducedExpressionofCholesterolTransportersFromMacrophagesbyLow-DoseEndotoxinUrmilaMaitra,LiwuLiObjective—Atherosclerosisischaracterizedasachronicinflammatoryconditionthatinvolvescholesteroldepositioninarteries.Togetherwithsc

2、avengerreceptorB1(SR-B1),theATP-bindingcassettetransportersABCA1andABCG1arethemajorcomponentsofmacrophagecholesterolefflux.Recentstudieshaveshownthatlow-gradeinflammationplaysadistinctregulatoryroleintheexpressionofSR-B1andABCA1/ABCG1.However,themechanismslink

3、inglow-gradeinflammationandcholesterolaccumulationarepoorlyunderstood.MethodsandResults—Usingprimarybone-marrow-derivedmacrophages,wedemonstratethatsubclinicallow-doselipopolysaccharidepotentlyreducestheexpressionofSR-B1andABCA1/ABCG1,aswellascholesterolefflux

4、frommacrophagesthroughinterleukin-1receptor-associatedkinase1andToll-interacting-protein.Low-doselipopolysaccharidedownregulatesthenuclearlevelsofretinoicacidreceptor-α,leadingtotheirreducedbindingtothepromotersofSR-B1andABCA1/ABCG1.Weobservethatglycogensyntha

5、sekinase3βactivationbylow-doselipopolysaccharidethroughinterleukin-1receptor-associatedkinase1andToll-interacting-proteinisresponsibleforreducedlevelsofretinoicacidreceptor-α,andreducedexpressionofSR-B1andABCA1/ABCG1.Interleukin-1receptor-associatedkinaseM,how

6、ever,counteractsthefunctionofinterleukin-1receptorassociatedkinase1.Conclusion—Collectively,ourdatarevealanovelintracellularnetworkregulatedbylow-doseendotoxemiathatdisruptscholesteroleffluxfrommacrophagesandleadstothepathogenesisofatherosclerosis.(Arterioscle

7、rThrombVascBiol.2013;33:24-33.)KeyWords:atherosclerosis◼low-gradeinflammation◼macrophages◼membranetransportersDownloadedfromhttp://ahajournals.orgbyonAugust7,2018◼molecularsignaltransductionsAtherosclerosisunderliesthepathogenesisofawiderangetraceamountofLPSse

8、eninchronicsubclinicalendotoxemiaofcardiovasculardiseases.Consequently,atherosclerosis(<100pg/mL)doesnotinduceacutecytokinestorm.Instead,andrelatedcardiovascularcomplicationsareamo