Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Annexin A1 modulates natural and glucocorticoid‐induced resolution of inflammation by enhancing neutrophil apoptosis | |
关键词: signaling cascade; dexamethasone; wortmannin; rolipram; Bcl‐; 2 family; | |
DOI : 10.1189/jlb.0112008 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
ThisstudyaimedatassessingwhetherAnxA1,adownstreammediatorfortheanti‐inflammatoryeffectsofGCs,couldaffectthefateofimmunecellsintissueexudates,usingLPS‐inducedpleurisyinBALB/cmice.AnxA1proteinexpressioninexudateswasincreasedduringnaturalresolution,asseenat48–72hpost‐LPS,aneffectaugmentedbytreatmentwithGCandassociatedwithmarkedpresenceofapoptoticneutrophilsinthepleuralexudates.ThefunctionalrelevanceofAnxA1wasdeterminedusinganeutralizingantibodyoranonspecificantagonistatFPR/ALXRs:eithertreatmentinhibitedbothspontaneousandGC‐inducedresolutionofinflammation.InjectionofAc2‐26(100μg,given4hintotheLPSresponse),anAnxA1‐activeN‐terminalpeptide,promotedactiveresolutionandaugmentedtheextentofneutrophilapoptosis.Suchaneffectwaspreventedbythepan‐caspaseinhibitorzVAD‐fmk.Mechanistically,resolutionofneutrophilicinflammationwaslinkedtocellapoptosiswithactivationofBaxandcaspase‐3andinhibitionofsurvivalpathwaysMcl‐1,ERK1/2,andNF‐κB.Thesenovelinvivodata,usingadynamicmodelofacuteinflammation,provideevidencethatAnxA1isamediatorofnaturalandGC‐inducedresolutionofinflammationwithprofoundeffectsonneutrophilapoptosis...
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201901239949856ZK.pdf | 628KB | download |