Deguelin Attenuates Allergic Airway Inflammation via Inhibition of NF-κb Pathway in Mice

被引:30
作者
Bao, Zhang [1 ]
Zhang, Pei [1 ]
Yao, Yinan [1 ]
Lu, Guohua [1 ]
Tong, Zhongkai [2 ]
Yan, Bing [1 ]
Tu, Lingfang [1 ]
Yang, Guangdie [1 ]
Zhou, Jianying [1 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Resp Dis, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China
[2] Ningbo 2 Hosp, Dept Resp Dis, Ningbo, Zhejiang, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2017年 / 13卷 / 04期
关键词
Asthma; Deguelin; Inflammation; NF-kappa B pathway; TSLP; INDUCED ASTHMATIC RESPONSES; MUC5AC EXPRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; AKT INHIBITOR; MURINE MODEL; ACTIVATION; APOPTOSIS; CYTOKINES; KINASE;
D O I
10.7150/ijbs.17238
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, resulting in a substantial economic burden on both patients and society. Deguelin, a constituent of the Leguminosae family, exhibits anti-proliferative and anti-inflammatory activities in cancer mice models via inhibiting phosphatidylinositol 3-kinases and the NF-kappa B pathway. We demonstrated that deguelin effectively reduced OVA-induced inflammatory cell recruitment, decreased lung tissue inflammation and mucus production, suppressed airway hyperresponsiveness, and inhibited serum immunoglobulin and Th2 cytokine levels in a dose-dependent manner in asthmatic mice. In addition, we found that deguelin reduced inflammatory gene expressions both in vivo and in vitro, which were closely associated with activation of the NF-kappa B signaling pathway. Thus, we further explored the underlying mechanisms of deguelin in normal human bronchial epithelial cells (BEAS-2B). Our results suggested that deguelin inhibited NF-kappa B binding activity by enhancing the ability of I kappa Ba to maintain NF-kappa B in an inactive form in the cytoplasm and preventing the TNF-alpha induced translocation of p65 to the nucleus. In conclusion, our research indicates that deguelin attenuates allergic airway inflammation via inhibition of NF-.B pathway in mice model and may act as a potential therapeutic agent for patients with allergic airway inflammation.
引用
收藏
页码:492 / 504
页数:13
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