Tumor necrosis factor α release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients 英文参考文献.docVIP

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Tumor necrosis factor α release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients 英文参考文献.doc

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Tumor necrosis factor α release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients 英文参考文献

Nabatianetal.ArthritisResearchTherapy2012,14:R1 /content/14/1/R1 RESEARCH ARTICLE OpenAccess Tumornecrosisfactorareleaseinperipheral bloodmononuclearcellsofcutaneouslupusand dermatomyositispatients AdamSNabatian1,2,3,MuhammadMBashir1,2,MariaWysocka2,MeenaSharma1,2 andVictoriaPWerth1,2* Abstract Introduction:SeveralstudieshavereportedthatTNFaissubstantiallyincreasedwithinskinlesionsofpatientswith discoidlupuserythematosus(DLE),subacutecutaneouslupuserythematosus(SCLE)anddermatomyositis(DM) comparedtocontrols.ElevatedTNFahasbeenreportedintheseraofsomepatientswithsystemiclupus erythematosus,DLEandSCLE,butnotintheseraofpatientswithDM.Becauseofthekeypathogenicroleof autoimmunityinthesediseases,inthisstudywesoughttoevaluateTNFaproductionbyareadilyavailablesource ofimmunecells(namely,peripheralbloodmononuclearcells(PBMCs))takenfromcontrolsandfrompatientswith cutaneouslupusorDM. Methods:FreshlyisolatedPBMCswereculturedovernight,andTNFaproteinaccumulationinconditioned mediumwasdetermined.Inaddition,flowcytometryusingcell-type-specificmarkerswasperformedtodetermine thesourcesofTNFa.One-wayanalysisofvarianceandDunnett’smultiplecomparisonstestwereperformedfor statisticalcomparisons. Results:AccumulationofTNFaproteininconditionedmediumcontainingPBMCsfromDLEpatients,butnotfrom SCLE,TLEorDMpatients,wassignificantlygreater(19-fold)thanthatfromcontrols(P0.001).InDLEPBMCs, increasedTNFawasproducedbycirculatingmonocytesandmyeloiddendriticcells(mDCs).ThemeanTNFa fluorescenceintensity,butnotthetotalnumber,ofbothmonocytesandmDCs(P0.01)fromDLEpatientswas significantlygreater(2.3-fold)thanthatofcontrols.Thereweresignificantlymore(13.3-fold)mDCswithintracellular TNFainbloodfromDLEpatients(P0.001)andDMpatients(P0.001)comparedtocontrols.Mostimportantly, apositivecorrelationwasseeninDLEpatientsbetweentheirdiseaseactivitymeasuredusingtheCutaneousLupus ErythematosusDiseaseAreaandSeverityIndexandTNFaproteinsecretion(r=0.61,P0.08). Conclusions:TNFaproteinproductionbyPBMCsisgreaterinDLEpati