Systemic lupus erythematosus(SLE)is a devastating autoimmune disorder associated with severe organ damage.The abnormality of T cell apoptosis is considered as an important pathogenetic mechanism of SLE.Norcantharidin(NCTD),a derivative of Cantharidin,is an efficacious anti-cancer drug by inhibiting cell proliferation and inducing cell apoptosis.Besides,NCTD has also been proved to protect the function of kidneys,while damaged renal function is the most important predictor of morbidity and mortality in SLE.All these suggest the potential effects of NCTD in SLE treatment.In this study we investigated whether NCTD exerted therapeutic effects in a mouse SLE model.Lupus prone female MRL/Ipr mice were treated with NCTD(1,2 mg·kg-1·d-1,ip)for 8 weeks.We showed that NCTD administration significantly decreased mortality rate,diminished the expression of anti-dsDNA IgG antibody,a diagnostic marker for SLE,as well as restored renal structure and function in MRL/Ipr mice.Moreover,NCTD administration dose-dependently inhibited lymphoproliferation and T cell accumulation in the spleens of MRL/Ipr mice.We further revealed that NCTD specifically inhibited DN T cell proliferation and Th17 cell differentiation both via blocking activation of signal transducer and activator of transcription 3(STAT3)signaling pathway.On the other hand,NCTD did not affect T cell apoptosis in MRL/Ipr mice.Taken together,our data suggest that NCTD may be as a promising therapeutic drug through targeting T cells for the treatment of SLE.

Li-jun Du;Yu-xiang Feng;Zhi-xing He;Lin Huang;Qiao Wang;Cheng-ping Wen;Yun Zhang

Institute of Basic Research in Clinical Medicine,College of Basic Medical Science,Zhejiang Chinese Medical University,Hangzhou 310053,China

中国药理学报（英文版）

[1]Li-jun Du;Yu-xiang Feng;Zhi-xing He;Lin Huang;Qiao Wang;Cheng-ping Wen;Yun Zhang-.Norcantharidin ameliorates the development of murine lupus via inhibiting the generation of IL-17 producing cells)[J].中国药理学报（英文版）,2022(06):1521-1533

Norcantharidin,Cantharidin,Ipr,lymphoproliferation

ameliorates,development,murine,lupus,via,inhibiting,generation,producing,cells,Systemic,erythematosus,SLE,devastating,autoimmune,disorder,associated,severe,organ,abnormality,apoptosis,considered,important,pathogenetic,mechanism,NCTD,derivative,efficacious,cancer,drug,by,inducing,Besides,has,also,been,proved,protect,function,kidneys,while,damaged,renal,most,predictor,morbidity,mortality,All,these,suggest,potential,effects,treatment,In,this,study,investigated,whether,exerted,therapeutic,mouse,model,Lupus,prone,female,MRL,mice,were,treated,weeks,We,showed,that,administration,significantly,decreased,diminished,expression,dsDNA,IgG,antibody,diagnostic,marker,well,restored,structure,Moreover,dose,dependently,inhibited,accumulation,spleens,further,revealed,specifically,Th17,differentiation,both,blocking,activation,transducer,activator,transcription,STAT3,signaling,pathway,On,other,hand,did,not,affect,Taken,together,our,data,may,promising,through,targeting

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