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
相关论文
共 52 条
[31]   Curcumin attenuates allergic airway inflammation by regulation of CD4+CD25+ regulatory T cells (Tregs)/Th17 balance in ovalbumin-sensitized mice [J].
Ma, Chunhua ;
Ma, Zhanqiang ;
Fu, Qiang ;
Ma, Shiping .
FITOTERAPIA, 2013, 87 :57-64
[32]   Preparation and characterization of bionanoemulsions for improving and modulating the antioxidant efficacy of natural phenolic antioxidant curcumin [J].
Malik, Parth ;
Ameta, R. K. ;
Singh, Man .
CHEMICO-BIOLOGICAL INTERACTIONS, 2014, 222 :77-86
[33]   Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress [J].
Motterlini, R ;
Foresti, R ;
Bassi, R ;
Green, CJ .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 28 (08) :1303-1312
[34]   Pathogenesis of airway inflammation in bronchial asthma [J].
Nakagome, Kazuyuki ;
Nagata, Makoto .
AURIS NASUS LARYNX, 2011, 38 (05) :555-563
[35]   Curcumin attenuates allergic airway inflammation and hyper-responsiveness in mice through NF-κB inhibition [J].
Oh, Se-Woong ;
Cha, Joo-Young ;
Jung, Ji-Eun ;
Chang, Beom-Chol ;
Kwon, Hyo-Jung ;
Lee, Bo-Ram ;
Kim, Dae-Yong .
JOURNAL OF ETHNOPHARMACOLOGY, 2011, 136 (03) :414-421
[36]   Optimal Management of Severe/Refractory Asthma [J].
Pakhale, Smita ;
Mulpuru, Sunita ;
Boyd, Matthew .
CLINICAL MEDICINE INSIGHTS-CIRCULATORY RESPIRATORY AND PULMONARY MEDICINE, 2011, 5 :37-47
[37]   Curcumin improves hypoxia induced dysfunctions in 3T3-L1 adipocytes by protecting mitochondria and down regulating inflammation [J].
Priyanka, Ariyapalli ;
Anusree, Sasidharan Suseela ;
Nisha, Vijayakumar Marykutty ;
Raghu, Kozhiparambil Gopalan .
BIOFACTORS, 2014, 40 (05) :513-523
[38]   Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications [J].
Ryter, SW ;
Alam, J ;
Choi, AMK .
PHYSIOLOGICAL REVIEWS, 2006, 86 (02) :583-650
[39]   Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages [J].
Saw, Constance Lay Lay ;
Yang, Anne Yuqing ;
Huang, Mou-Tuan ;
Liu, Yue ;
Lee, Jong Hun ;
Khor, Tin Oo ;
Su, Zheng-Yuan ;
Shu, Limin ;
Lu, Yaoping ;
Conney, Allan H. ;
Kong, Ah-Ng Tony .
CELL AND BIOSCIENCE, 2014, 4
[40]   The transcription factor NF-E2-related Factor 2 (Nrf2): a protooncogene? [J].
Shelton, Phillip ;
Jaiswal, Anil K. .
FASEB JOURNAL, 2013, 27 (02) :414-423