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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
Author(s) -
Wan Jie,
Cao Yuwen,
Abdelaziz Mohamed Hamed,
Huang Lan,
Kesavan Dinesh Kumar,
Su Zhaoliang,
Wang Shengjun,
Xu Huaxi
Publication year - 2019
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12752
Subject(s) - apoptosis , rac1 , airway , phagocytosis , respiratory tract , microbiology and biotechnology , immunology , biology , cancer research , medicine , respiratory system , signal transduction , biochemistry , anatomy , surgery
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 ( NSC 23766) 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 si RNA 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.