Investigation of the differential potentials of TLR agonists to elicit uveitis in mice

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

关键词: PAMPs;    cytokines;    iritis;    leukocyte chemotaxis;   

DOI  :  10.1189/jlb.0511249

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TLRsarecriticalforhostdefenseandinnateimmunity.EmergingevidencealsosupportsaroleforTLRsinmanychronicinflammatorydiseases,includinginflammatoryeyedisease,knownasuveitis.TheactivationofTLR4byendotoxininducesastandardmodelofmurineuveitis.HowactivationofadditionalTLRsinfluencestheonsetand/orseverityofanterioruveitishasnotbeenexamined.WesoughttoelucidatethepotentialofTLRs(TLR1/2,TLR2/6,TLR3,TLR4,TLR5,TLR7/8,andTLR9)totriggeruveitisinmice.Directlystimulatediris/ciliarybodyexplantsdemonstratedamarkedincreaseinproductionofinflammatorycytokinesTNF‐α,IL‐6,IP‐10/CXCL10,MCP‐1,andKCwithrelativelylittleproductionofIFN‐γ,IL‐10,IL‐12p40,IL‐12p70,IL‐17,IL‐1β,IL‐4,orRANTES.Thecytokine‐responseprofileswerecomparableamongsttheTLRagonists,albeitsomedifferenceswerenoted,suchasgreaterIP‐10productionfollowingTLR3activation.Intra‐ocularinjectionofTLRagonistsincreasedleukocyteinteractionswiththeendotheliumoftheirisvasculatureandresultedinchemotaxisintotheiristissue.AssessmentofleukocyticresponsesbyivtvideomicroscopyandhistologyrevealedquantitativedifferencesamongstresponsestotheTLRagonistswithrespecttothetimingandnumbersofrolling,adhering,iris‐infiltrating,andaqueoushumor‐infiltratingcells,alongwithcytokinelevelsinvivo.Ourdatademonstratetheeyeˈsresponsivenesstoadiversearrayofmicrobialproducts,whichactivatesTLRs,andrevealdifferencesinrelativecellularresponseamongthevariousTLRagonistsinvivo...

【 授权许可】

CC BY