抑制SOCS3的表达可减弱哮喘患者体内嗜酸性粒细胞的作用
2015/05/22
摘要
嗜酸性粒细胞是哮喘中最主要的炎症细胞之一。嗜酸性粒细胞可通过表达和分泌多种分子发挥一系列作用。之前的研究结果显示,哮喘患者外周血细胞中分离出来的嗜酸性粒细胞可表达高水平的细胞信号转导抑制因子3(SOCS3)。本研究旨在通过静默哮喘患者嗜酸性粒细胞中的SOCS3基因以更好地研究其对嗜酸性粒细胞功能的抑制作用。SOCS3 siRNA处理可以显著降低哮酸性粒细胞SOCS3基因的表达水平,从而进一步抑制了调节性转录因子GATA-3和FoxP3的表达以及白介素(IL)-10水平;进而,还观察到STAT3磷酸化的增加。此外,嗜酸性粒细胞中SOCS3基因的敲除抑制了其迁移、粘附和脱颗粒作用。因此,SOCS3可能在哮喘发生过程中发挥调节嗜酸性粒细胞从骨髓中迁移至肺组织的重要作用。
(杨冬 审校)
Int J Mol Sci. 2015 Mar 10;16(3):5434-5451.
SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients.
Zafra MP1,2, Cañas JA3, Mazzeo C4,5, Gámez C6,7, Sanz V8,9, Fernández-Nieto M10,11, Quirce S12,13,Barranco P14,15, Ruiz-Hornillos J16, Sastre J17,18, Del Pozo V19,20.
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ABSTRACT
Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.
Int J Mol Sci. 2015 Mar 10;16(3):5434-5451.
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痰液转录组学的无创分析可区分哮喘患者的临床表型
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CCL2/CCR2依赖的Th17细胞(非Tc17细胞)在哮喘小鼠模型的肺中的募集