Endotoxin‐induced uveitis is primarily dependent on radiation‐resistant cells and on MyD88 but not TRIF

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

关键词: lipopolysaccharide;    iritis;    TLR4;    cytokines;   

DOI  :  10.1189/jlb.0111036

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TLR4activationbyLPS(endotoxin)ismediatedbytheMyD88andTRIFintracellularsignalingpathways.WedeterminedtherelativeactivationofthesepathwaysinmurineoculartissueafterLPSexposure.Additionally,weexploredwhetherBM‐derivedornon‐BM‐derivedcellswerethemajorcontributorstoEIU.MicedeficientinTRIForMyD88andtheircongenic(WT)controlsreceived250ngultrapureLPSivtat0h.Ocularinflammationwasassessedbyhistologicalanalysisat4,6,and24h,andadditionally,inMyD88−/−mice,intravitalmicroscopywasperformedat4hand6htoassessadherent,rolling,andinfiltratingcellsintheirisvasculatureandtissue.CytokinesassociatedwiththeMyD88andTRIFintracellularsignalingpathwayswereanalyzedinoculartissueat4h.BMchimericmice(WT→WT,TLR4−/−→WT,WT→TLR4−/−)received250ngLPSbyivtinjection,andoculartissueswereexaminedbyhistologyat6h.LackofMyD88resultedinamarkedlydiminishedcellularresponseandreducedproductionofMyD88‐relatedcytokines4hpost‐LPStreatment.Incontrast,lackofTRIFledtoreducedproductionofTRIF‐relatedcytokinesandnochangeinthecellularresponsetoLPS.Therefore,theMyD88pathwayappearstobethedominantTLR4pathwayinEIU.OnlyWT→TLR4−/−chimericmicewereresistanttoEIU,andthissuggests,surprisingly,thatnon‐BM‐derived(radiation‐resistant)cellsintheeyeplayagreaterrolethanBM‐derivedcells...

【 授权许可】

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