Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells, which may be associated with airway hyper-responsiveness in asthma
Downregulated Rac1 promotes apoptosis and inhibits the clearance of apoptotic cells in airway epithelial cells, which may be associated with airway hyper-responsiveness in asthma
复制标题
下调Rac1促进细胞凋亡并抑制气道上皮细胞凋亡细胞的清除，这可能与哮喘气道高反应性有关
DOI：
10.1111/sji.12752
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发表时间：
2019
影响因子：
3.7
通讯作者：
Xu Huaxi
中科院分区：
文献类型：
--
作者：
Wan Jie;Cao Yuwen;Abdelaz Mohamed Hamed;Huang Lan;Kesava Dinesh Kumar;Su Zhaoliang;Wang Shengjun;Xu Huaxi
气道凋亡细胞的积累可能是引起气道超反应性（AHR）的重要因素。凋亡细胞能否及时清除与哮喘的发生和病程有关。近年来的研究表明，Rac1参与了许多细胞生物学活动，包括凋亡细胞的形成和消除。本研究在分析哮喘小鼠气道局部细胞及相关因素的基础上，评估了Rac1在气道上皮细胞或吞噬细胞中的表达，并分析了其与凋亡发生率或凋亡细胞清除的关系。我们的数据显示，哮喘小鼠中Rac1的表达水平明显下降，而IL - 33的表达水平明显升高。50 μmol/L姜黄素刺激气道上皮细胞系24 ~ 48小时；50%以上的细胞发生凋亡，其中晚期凋亡约占20%。Rac1抑制剂（NSC23766）可增强细胞凋亡作用。此外，应用Rac1抑制剂或特异性siRNA后，上皮细胞或巨噬细胞的吞噬和迁移能力呈剂量依赖性增加，阻断Rac1后IL - 33的表达水平同时升高。提示哮喘中Rac1的下调可能导致气道上皮细胞凋亡，影响凋亡细胞的清除，导致凋亡细胞在呼吸道聚集，参与AHR。
The accumulation of airway apoptotic cells may be an important factor causing airway hyper‐responsiveness (AHR). Whether the apoptotic cells can be promptly removed is related to the occurrence and course of asthma. In recent years, studies have shown that Rac1 is involved in many cellular biological activities including the formation and elimination of apoptotic cells. In this study, based on the analysis of airway local cells and related factors in asthmatic mice, we evaluated the expression of Rac1 in airway epithelial cells or phagocytes and analysed its relationship with the incidence of apoptosis or scavenging of apoptotic cells. Our data showed that the expression level of Rac1 in asthmatic mice decreased significantly, while the expression of IL‐33 increased obviously. The airway epithelial cell line was stimulated by curcumin at 50 μmol/L for 24‐48 hours; more than 50% of the cells were apoptotic, and of which, about 20% were late apoptosis. Rac1 inhibitor (NSC23766) can enhance the apoptosis effect. In addition, the ability of phagocytosis and migration in the epithelial cells or macrophages was increased following the application of Rac1 inhibitors or specific siRNA in a dose‐dependent manner, and the expression level of IL‐33 was simultaneously increased after blocking Rac1. It is suggested that the down regulation of Rac1 in asthma may contribute to the apoptosis of airway epithelial cells and affect the clearance of apoptotic cells, which will lead to the aggregation of the apoptotic cells in the respiratory tract and participate in AHR.