Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse.
Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse.
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DOI：
10.1186/s12959-021-00314-6
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发表时间：
2021-08-28
影响因子：
3.1
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Tong H;Ding Y;Gui X;Sun Z;Wang G;Zhang S;Xu Z;Wang X;Xu X;Ju W;Li Y;Li Z;Zeng L;Xu K;Qiao J
免疫性血小板减少症（ITP）是一种自身免疫性疾病，其特征是免疫介导的血小板破坏导致血小板计数降低。富马酸二甲酯（DMF）具有免疫抑制作用，广泛应用于多种自身免疫性疾病的治疗。然而，它是否改善ITP尚不清楚。本研究旨在评价DMF是否对小鼠ITP具有预防作用。小鼠腹腔注射DMF（30、60或90 mg/kg体重），然后注射大鼠抗小鼠整合素GPIIb/CD 41抗体以诱导ITP。分离外周血测定血小板计数，提取脾脏单个核细胞测定Th 1、Treg细胞沿着，免疫组化法检测血浆IFN-γ、TGFβ-1水平及脾脏CD 68表达。此外，培养巨噬细胞系RAW 264. 7，并用DMF处理，然后分析细胞凋亡和周期，以及FcγRI、FcγRIIb和FcγRIV mRNA的表达。DMF可显著抑制抗血小板抗体诱导的血小板破坏，降低ITP小鼠脾脏中Th 1细胞、T-bet和IFN-γ的表达，上调Treg细胞、Foxp 3和TGF-β1的表达，降低CD 68的表达。DMF处理后RAW264.7细胞S期阻滞，凋亡增加，FcγRI和FcγRIV表达下调。同时，DMF体外处理后，细胞周期蛋白D1和E2的表达降低，Bcl-2的表达降低，Bax的表达增加，caspase-3的活化增强。总之，DMF可能通过促进细胞凋亡来防止ITP小鼠抗体介导的血小板破坏，表明其可能用作治疗ITP的新方法。在线版本包含补充材料，可通过10.1186/s12959-021-00314-6获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12959-021-00314-6.
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影响因子：
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作者：
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