| Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
| Down‐regulation of survivin alleviates experimental arthritis | |
| 关键词: T cells; Blimp‐; 1; p53; Treg; erosions; synovitis; | |
| DOI : 10.1189/jlb.3A0714-317R | |
| 学科分类：生理学 | |
| 来源: Federation of American Societies for Experimental Biology | |
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【 摘 要 】
Survivinisaproto‐oncogenethatregulatescelldivisionandapoptosis.Itisamolecularmarkerofcancer.Recently,survivinhasemergedasafeatureofRA,associatedwithseverejointdamageandpoortreatmentresponse.Thepresentstudyexaminedifinhibitionofsurvivinaffectsexperimentalarthritis,whichwasinducedinmBSA‐immunizedmicebyaninjectionofmBSAinthekneejointordevelopedspontaneouslyincollagentypeII‐immunizedmice.TheinhibitionofsurvivintranscriptionbyalentivirusshRNAconstructalleviatedjointinflammationandreducedbonedamage.Theinhibitionofsurvivinreducedthelevelsofmetalloproteinases,β‐catenin,andvimentin,limitingtheinvasivecapacityofsynovia,whilenoinhibitionofosteoclastogenesiscouldbefound.Theinhibitionofsurvivinledtoap53‐independentreductionofTcellproliferationandfavoredthetranscriptionandactivityofBlimp‐1,whichlimitedIL‐2productionandfacilitatedformationofregulatoryFoxp3+CD4+andeffectorCD8+Tcells.Thestudyshowsthattheinhibitionofsurvivinissufficienttoreducejointinflammationandbonedamageinpreclinicalmodelsofarthritis.Antiarthriticeffectsofsurvivininhibitionarerelatedtop53‐independentcontroloflymphocyteproliferation...
【 授权许可】
CC BY
【 预 览 】
| Files | Size | Format | View |
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| RO201904043273410ZK.pdf | 2082KB |  download |
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