SM934 Treated Lupus-Prone NZB×NZW F1 Mice by Enhancing Macrophage Interleukin-10 Production and Suppressing Pathogenic T Cell Development 英文参考文献.docVIP

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SM934 Treated Lupus-Prone NZB×NZW F1 Mice by Enhancing Macrophage Interleukin-10 Production and Suppressing Pathogenic T Cell Development 英文参考文献.doc

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SM934 Treated Lupus-Prone NZB×NZW F1 Mice by Enhancing Macrophage Interleukin-10 Production and Suppressing Pathogenic T Cell Development 英文参考文献

SM934TreatedLupus-ProneNZB6NZWF1Miceby EnhancingMacrophageInterleukin-10Productionand SuppressingPathogenicTCellDevelopment Li-FeiHou1.,Shi-JunHe1.,XinLi1,Chun-PingWan2,YangYang2,Xiao-HuiZhang2,Pei-LanHe1 ,Yu Zhou1,Feng-HuaZhu1,Yi-FuYang2,YingLi3,WeiTang1,Jian-PingZuo1,2* 1LaboratoryofImmunopharmacology,StateKeyLaboratoryofDrugResearch,ShanghaiInstituteofMateriaMedica,ChineseAcademyofSciences,Shanghai,People’s RepublicofChina,2LaboratoryofImmunologyandVirology,ShanghaiUniversityofTraditionalChineseMedicine,Shanghai,People’sRepublicofChina,3Departmentof SyntheticChemistry,ShanghaiInstituteofMateriaMedica,ChineseAcademyofSciences,Shanghai,People’sRepublicofChina Abstract Background: Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmunediseases.ThisstudywasdesignedtoexaminethetherapeuticeffectsandunderlyingmechanismsofSM934,a water-solubleartemisininanalogue,onlupus-pronefemaleNZB6NZWF1mice. Methodology/Principal Findings: NZB/W F1 mice were treated orally with SM934 for 3 or 6 months respectively to investigatetheeffectonclinicalmanifestationsandimmunologicalcorrelates.TofurtherexplorethemechanismsofSM934, ovalbumin(OVA)-immunizedorinterferon(IFN)-c-elicitedC57BL/6micewereused.Invivo,treatmentwithSM934for3or6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F1 mice. ClinicalimprovementwasaccompaniedwithdecreasedTh1-relatedanti-double-strandDNA(dsDNA)IgG2aandIgG3Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4+ T cells, while enhancing the development of regulatory T cells in NZB/W F1 mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F1 mice, OVA-immunized C57BL/6 mice and IFN-c-elicited C57BL/6 mice. In vitro , SM934 enhancedIL-10productionfromprimarymac