Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4(+)Foxp3(+) Regulatory T Cells Differentiation.
Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4(+)Foxp3(+) Regulatory T Cells Differentiation.
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Apremilast 通过抑制 Th1 和 Th17 细胞并增强 CD4 Foxp3 调节性 T 细胞分化来改善实验性关节炎
DOI：
10.3389/fimmu.2018.01662
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zheng SG
中科院分区：
文献类型：
--
作者：
Chen W;Wang J;Xu Z;Huang F;Qian W;Ma J;Wee HB;Lewis GS;June RR;Schafer PH;Lin J;Zheng SG
阿普米司特是一种新型的磷酸二酯酶4(PDE4)抑制剂，可抑制免疫和炎症反应。我们在II型胶原(CII)诱导的关节炎(CIA)小鼠模型上评价了阿普司特的抗炎作用。为了确定阿普利司特是否能改善该模型的关节炎发病，在CII免疫后第14天给予阿普米司特口服。骨侵蚀通过组织学和显微计算机断层扫描分析进行测量。用酶联免疫吸附试验检测小鼠血清中抗CII抗体水平，用流式细胞仪检测淋巴结中Th1、Th1 细胞和Th4+Foxp3+调节性T细胞。将人软骨和类风湿关节炎(RA)滑膜成纤维细胞(RASF)植入严重联合免疫缺陷小鼠RA模型，研究阿普利司特在体内抑制RASF介导的软骨破坏中的作用。与未治疗组和赋形剂对照组相比，我们发现在CIA模型中，阿普利司特治疗推迟了关节炎的发生，并降低了关节炎评分。阿司匹林治疗组血清总免疫球蛋白Ig G、Ig G1、Ig G2a、Ig G2b均降低。此外，CT分析表明，阿普司特能显著阻止CIA小鼠骨质侵蚀的发展。此外，阿普利司特组Th1 7 细胞和Th1 细胞频率显著降低，而Treg细胞频率显著升高。阿普司特大剂量(25 mg/kg)治疗效果优于小剂量(5 mg/kg)。阿普司特治疗降低了RASF的迁移能力及其对软骨的破坏作用。与模型组相比，阿普利司特治疗显著降低了原始种植体和对侧种植体模型中RASF侵袭软骨的评分。我们的数据表明阿普米司特在治疗自身免疫性关节炎和防止CIA模型中的骨侵蚀方面是有效的，暗示了其在RA患者中的治疗潜力。
Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells’ frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA.
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影响因子：
7.3
作者：
Peng WX;Zhu SL;Zhang BY;Shi YM;Feng XX;Liu F;Huang JL;Zheng SG
通讯作者：
Zheng SG
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DOI：
10.4049/jimmunol.1000598
发表时间：
2010-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhou X;Kong N;Wang J;Fan H;Zou H;Horwitz D;Brand D;Liu Z;Zheng SG
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影响因子：
24.1
作者：
Liu, Yan;Pan, Yun Feng;Zheng, Song Guo
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影响因子：
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作者：
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影响因子：
24.1
作者：
Zhu, Shang-ling;Huang, Jian-lin;Zheng, Song Guo
通讯作者：
Zheng, Song Guo