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  2. Protective effect of dihydroartemisinin in inhibiting senescence of myeloid-derived suppressor cells from lupus mice via Nrf2/HO-1 pathway

Protective effect of dihydroartemisinin in inhibiting senescence of myeloid-derived suppressor cells from lupus mice via Nrf2/HO-1 pathway

  • Free Radic Biol Med. 2019 Nov 1;143:260-274. doi: 10.1016/j.freeradbiomed.2019.08.013.
Dan Li 1 Jingjing Qi 1 Jiali Wang 1 Yuchen Pan 1 Jingman Li 1 Xiaoyu Xia 1 Huan Dou 2 Yayi Hou 3
Affiliations

Affiliations

  • 1 The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, PR China.
  • 2 The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, PR China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, PR China. Electronic address: douhuan@nju.edu.cn.
  • 3 The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, PR China; Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, PR China. Electronic address: yayihou@nju.edu.cn.
Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by multi-organ injury. However, whether myeloid-derived suppressor cells (MDSCs) senescence exists and participates in SLE pathogenesis remains unclear. And whether dihydroartemisinin (DHA) attenuates the symptoms of SLE via relieving MDSCs senescence remains elusive. In the present study, we measured the senescence of MDSCs in SLE using SA-β-gal staining, senescence-associated secretory phenotype (SASP) and Western blot analysis of aging-related protein P21, P53 and P16. We identified that the MDSCs senescence promoted the SLE progress by adaptive transfer MDSCs assays. Meanwhile, we further showed DHA ameliorated the symptoms of pristane-induced lupus by histopathological detection, Western blot analysis, immunofluorescence, QPCR and flow cytometry analysis. DHA reversed MDSCs senescence by detecting SA-β-gal staining, senescence-associated secretory phenotype (SASP) and Western blot analysis of aging-related protein P21, P53 and P16. Furthermore, mechanistic analysis indicated that the inhibitory effect of DHA on MDSCs senescence was blocked by ML385, the specific antagonist of Nrf2, which revealed that the effect of DHA on MDSCs senescence was dependent on the induction of Nrf2/HO-1 pathway. Of note, we revealed that DHA inhibited MDSCs senescence to ameliorate the SLE development by adaptive transfer DHA-treated MDSCs assays. In conclusion, MDSCs senescence played a vital role in the pathogenesis of SLE, and DHA attenuated the symptoms of SLE via relieving MDSCs aging involved in the induction of Nrf2/HO-1 pathway.

Keywords

Dihidroartemisinin; MDSCs; Nrf2; Senescence; Systemic lupus erythematosus; TLR7.

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