We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regi...We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.展开更多
Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artem...Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artemisininbased therapy for malaria. Beyond antimalaria, artemisinin and its derivatives are also being investigated in diseases like schistosomiasis, viral infection, cancers and inflammation. Over the past decades, the anti-inflammatory and immunomodulatory effects of artemisinin drugs have been comprehensively studied. In this article, we will briefly describe the development of artemisinin drugs, especially novel artemisinin derivatives, in the treatment of autoimmune diseases.展开更多
文摘We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.
基金supported by the National Natural Science Foundation of China(812735248127352581322049)the National Basic Research Program of China(2014CB541906)
文摘Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artemisininbased therapy for malaria. Beyond antimalaria, artemisinin and its derivatives are also being investigated in diseases like schistosomiasis, viral infection, cancers and inflammation. Over the past decades, the anti-inflammatory and immunomodulatory effects of artemisinin drugs have been comprehensively studied. In this article, we will briefly describe the development of artemisinin drugs, especially novel artemisinin derivatives, in the treatment of autoimmune diseases.
