Bufotalin ameliorates experimental Sjögren’s syndrome development by inhibiting Th17 generation

Abstract

Chronic inflammatory autoimmune disease Sjögren’s syndrome (SS) is characterized by the reduced secretion of exocrine glands, suggesting strategies targeting inflammation to be a potential option for SS therapy. Bufotalin, an active constituent of Bufadienolides, exerts potent antitumor effects with unknown effects on autoimmune diseases including SS. This study aims to investigate whether bufotalin possesses therapeutic potentials to SS and the underlying mechanisms. The experimental Sjögren’s syndrome (ESS) murine model was constructed by SG-immunization and murine naïve CD4+ T cells were cultured under Th17 polarization conditions with or without low doses of bufotalin treatment. Saliva flow rate was measured, and flow cytometry was applied to analyze T cell subpopulations. ELISA was conducted to determine the levels of targeted inflammatory cytokines. Bufotalin-treated ESS mice showed higher saliva flow rates, lower serum levels of autoantibodies (anti-M3R and anti-SSA IgG), lower serum levels of pro-inflammatory cytokines, as well as lower Th17 cell population from spleens and cervical lymph nodes. Additionally, in vitro study showed that bufotalin inhibits Th17 polarization and secretion of cytokines IL-17 and IFN-γ. Bufotalin at a low dose significantly ameliorates ESS development, possibly via inhibiting pro-inflammatory Th17 population and secretion of inflammatory cytokines during ESS pathogenesis.

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Yang Huang and Guangxia Yang contributed equally to this work. Guangxia Yang, Jing Fei, and Yingyi Wu conceptualized the study and conducted the literature review for all databases. Yang Huang, Guangxia Yang, Jing Fei, and Yingyi Wu performed all statistical analyses. Juzhen Yan drafted the paper. Juzhen Yan provided useful additional intellectual content into the draft and contributed to the writing of the final version of the paper.

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Correspondence to Juzhen Yan.

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Huang, Y., Yang, G., Fei, J. et al. Bufotalin ameliorates experimental Sjögren’s syndrome development by inhibiting Th17 generation. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1977–1985 (2020). https://doi.org/10.1007/s00210-020-01817-1

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Keywords

  • Sjögren’s syndrome
  • Bufotalin
  • Inflammation
  • Th17 cells
  • Cytokines