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免疫性血小板减少症患者中NLRP3表达升高。

Elevated expression of NLRP3 in patients with immune thrombocytopenia.

作者信息

Qiao Jianlin, Liu Yun, Li Xiaoqian, Xia Yuan, Wu Yulu, Li Depeng, Li Hongchun, Ma Ping, Zhu Feng, Li Zhenyu, Xu Kailin, Zeng Lingyu

机构信息

Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, 99, West Huaihai Rd, Quanshan District, Xuzhou, 221002, Jiangsu Province, China.

Blood Diseases Institute, Xuzhou Medical College, Xuzhou, 221002, China.

出版信息

Immunol Res. 2016 Apr;64(2):431-7. doi: 10.1007/s12026-015-8686-5.

Abstract

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, which is characterized by dysregulation of T cell-mediated autoimmunity. NLRP3, a largest and mostly well-studied inflammasome, has been shown to be important in the regulation of adaptive immune response, especially in T cell response. Given the closely association of imbalance of T cell response with ITP, whether NLRP3 is involved in the pathogenesis of ITP remains poorly understood. In this study, 69 active ITP patients, 21 ITP in remission and 24 age- and gender-matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma, which were used to measure mRNA level of NLRP3 and adaptor protein ASC by quantitative real-time PCR and IL-18 plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of NLRP3 expression. Our results showed a significantly higher expression of NLRP3, ASC and plasma IL-18 level in patients with active ITP when compared to control. The expression of NLRP3, ASC and plasma IL-18 level was significantly lower in patients in remission than that in active ITP, and no difference was observed when compared to control. Furthermore, a significantly positive correlation of NLRP3 with ASC was observed in patients with active ITP. In conclusion, increased expression of NLRP3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a new strategy in the treatment of ITP.

摘要

免疫性血小板减少症(ITP)是一种异质性自身免疫性疾病,其特征在于T细胞介导的自身免疫失调。NLRP3是最大且研究最充分的炎性小体,已被证明在适应性免疫反应的调节中起重要作用,尤其是在T细胞反应中。鉴于T细胞反应失衡与ITP密切相关,NLRP3是否参与ITP的发病机制仍知之甚少。在本研究中,纳入了69例活动性ITP患者、21例缓解期ITP患者以及24例年龄和性别匹配的健康对照。从ITP患者和对照中分离外周血单个核细胞(PBMC)以提取RNA和血浆,用于通过定量实时PCR测量NLRP3和衔接蛋白ASC的mRNA水平,并通过ELISA测量血浆IL-18水平。同时,也从PBMC中提取蛋白质用于NLRP3表达的蛋白质印迹分析。我们的结果显示,与对照相比,活动性ITP患者中NLRP3、ASC的表达及血浆IL-18水平显著更高。缓解期ITP患者中NLRP3、ASC的表达及血浆IL-18水平显著低于活动性ITP患者,与对照相比无差异。此外,在活动性ITP患者中观察到NLRP3与ASC呈显著正相关。总之,NLRP3表达增加与ITP的发病机制相关,以其为治疗靶点可能是ITP治疗的一种新策略。

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