Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway

被引:75
|
作者
Liu, Liyun [1 ]
Shang, Yunxiao [1 ]
Li, Miao [1 ]
Han, Xiaohua [1 ]
Wang, Jia [1 ]
Wang, Juan [1 ]
机构
[1] China Med Univ, Dept Pediat, Shengjing Hosp, Shenyang 110004, Peoples R China
关键词
asthma; curcumin; Nrf2; HO-1; pathway; pro-inflammation cytokine; RAW264; 7; cell; siRNA; HEME OXYGENASE-1; GENE-EXPRESSION; PROTECTS; INJURY; NRF2; INDUCTION; APOPTOSIS; MICE; ANTIOXIDANT; KINASE;
D O I
10.1111/1440-1681.12384
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-B and inhibitory B/p-inhibitory B levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-, interleukin (IL)-1, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-B and p-inhibitory B levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced in dose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-, IL-1, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.
引用
收藏
页码:520 / 529
页数:10
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