Amelioration of Lupus Nephritis by Serum Amyloid P Component Gene Therapy with Distinct Mechanisms Varied from Different Stage of the Disease 英文参考文献.docVIP

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Amelioration of Lupus Nephritis by Serum Amyloid P Component Gene Therapy with Distinct Mechanisms Varied from Different Stage of the Disease 英文参考文献.doc

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Amelioration of Lupus Nephritis by Serum Amyloid P Component Gene Therapy with Distinct Mechanisms Varied from Different Stage of the Disease 英文参考文献

AmeliorationofLupusNephritisbySerumAmyloidP ComponentGeneTherapywithDistinctMechanisms VariedfromDifferentStageoftheDisease WeijuanZhang1.,JinWu1.,BinQiao1,WeiXu1,SidongXiong1,2* 1InstituteforImmunobiologyandDepartmentofImmunology,ShanghaiMedicalCollege,FudanUniversity,Shanghai,People’sRepublicofChina,2InstitutesofBiology andMedicalSciences,SoochowUniversity,Suzhou,People’sRepublicofChina Abstract Background:OurpreviousstudyrevealedthatadministrationofsyngeneicfemaleBALB/cmicewithexcessiveselfactivated lymphocyte-derivedDNA(ALD-DNA)couldinducesystemiclupuserythematosus(SLE)disease,indicatingthatoverloadof self-DNA might exceed normal clearance ability and comprise the major source of autoantigens in lupus mice. Serum amyloidPcomponent(SAP),anacute-phaseserumproteinwithbindingreactivitytoDNAinmice,wasprovedtopromote the clearance of free DNA and prevent mice against self-antigen induced autoimmune response. It is reasonable to hypothesizethatSAPtreatmentmightcontributetoalleviationofSLEdisease,whereasitsroleinALD-DNA-inducedlupus nephritisisnotfullyunderstood. Methodology/PrincipalFindings:TheratiosofSAPtoDNAsignificantlydecreasedandwerenegativelycorrelatedwiththe titers of anti-dsDNA antibodies in ALD-DNA-induced lupus mice, indicating SAP was relatively insufficient in lupus mice. Herein a pcDNA3-SAP plasmid (pSAP) was genetically constructed and intramuscularly injected into BALB/c mice. It was foundthat SAPprotein purifiedfromthe serumof pSAP-treated mice bound efficiently toALD-DNA andinhibited ALD- DNA-mediatedinnateimmuneresponseinvitro.TreatmentofALD-DNA-inducedlupusmicewithpSAPintheearlystageof SLEdiseasewiththeonsetofproteinuriareversedlupusnephritisviadecreasinganti-dsDNAautoantibodyproductionand immunecomplex(IC)deposition.FurtheradministrationofpSAPinthelatestageofSLEdiseasethathadestablishedlupus nephritisalleviatedproteinuriaandamelioratedlupusnephritis.ThistherapeuticeffectofSAPwasnotonlyattributableto thedecreasedlevelsofanti-dsDNAautoantibodies,b