2. Academic Validation
  3. Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse

Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse

  • Thromb J. 2021 Aug 28;19(1):61. doi: 10.1186/s12959-021-00314-6.
Huan Tong  # 1 2 3,  Yangyang Ding  # 1 2 3,  Xiang Gui  # 1 2 3,  Zengtian Sun 1 2 3,  Guozhang Wang 1 2 3,  Sixuan Zhang 1 2 3,  Zhengqing Xu 1 2 3,  Xiamin Wang 1 2 3,  Xiaoqi Xu 1 2 3,  Wen Ju 1 2 3,  Yue Li 4,  Zhenyu Li 1 2 3,  Lingyu Zeng 5 6 7 8,  Kailin Xu 9 10 11,  Jianlin Qiao 12 13 14
Affiliations

Affiliations

  • 1 Blood Diseases Institute, Xuzhou Medical University, 84 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China.
  • 2 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
  • 3 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, 221002, China.
  • 4 School of Medical Technology, Xuzhou Medical University, Xuzhou, 221002, China.
  • 5 Blood Diseases Institute, Xuzhou Medical University, 84 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China. [email protected].
  • 6 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 7 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, 221002, China. [email protected].
  • 8 School of Medical Technology, Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 9 Blood Diseases Institute, Xuzhou Medical University, 84 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China. [email protected].
  • 10 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 11 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, 221002, China. [email protected].
  • 12 Blood Diseases Institute, Xuzhou Medical University, 84 West Huaihai Road, Quanshan District, Xuzhou, 221002, Jiangsu, China. [email protected].
  • 13 Department of Hematology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China. [email protected].
  • 14 Key Laboratory of Bone Marrow Stem Cell, Jiangsu Province, Xuzhou, 221002, China. [email protected].
  • # Contributed equally.
PMID: 34454532 DOI: 10.1186/s12959-021-00314-6
Abstract

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice.

Methods: DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse Integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell Apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA.

Results: DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased Apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and Caspase-3 activation.

Conclusions: In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting Apoptosis, indicating that it might be used as a new approach for the treatment of ITP.

Keywords

Apoptosis; Cell cycle; Dimethyl fumarate; Immune thrombocytopenia; Macrophage.

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