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Down‐regulation of survivin alleviates experimental arthritis

机译:Survivin的下调可减轻实验性关节炎

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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...
机译:Survivinisaproto-oncogenethatregulatescelldivisionandapoptosis.Itisamolecularmarkerofcancer.Recently,survivinhasemergedasafeatureofRA,associatedwithseverejointdamageandpoortreatmentresponse.Thepresentstudyexaminedifinhibitionofsurvivinaffectsexperimentalarthritis,whichwasinducedinmBSA-immunizedmicebyaninjectionofmBSAinthekneejointordevelopedspontaneouslyincollagentypeII-immunizedmice.TheinhibitionofsurvivintranscriptionbyalentivirusshRNAconstructalleviatedjointinflammationandreducedbonedamage.Theinhibitionofsurvivinreducedthelevelsofmetalloproteinases,β连环蛋白,andvimentin,limitingtheinvasivecapacityofsynovia,whilenoinhibitionofosteoclastogenesiscouldbefound.Theinhibitionofsurvivinledtoap53-independentreductionofTcellproliferationandfavoredthetranscriptionandactivityofBlimp-1,whichlimitedIL-2productionandfacilitatedformationofregulatoryFoxp3 + CD4 + andeffectorCD8 + T细胞。研究表明,在临床前模型中,对存活率的抑制作用不足以导致炎性炎症和结合损伤。抑制生存的抗关节炎作用与淋巴细胞增殖的前53独立控制有关...

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