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
[1]   Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature [J].
Anand, Preetha ;
Thomas, Sherin G. ;
Kunnumakkara, Ajaikumar B. ;
Sundaram, Chitra ;
Harikumar, Kuzhuvelil B. ;
Sung, Bokyung ;
Tharakan, Sheeja T. ;
Misra, Krishna ;
Priyadarsini, Indira K. ;
Rajasekharan, Kallikat N. ;
Aggarwal, Bharat B. .
BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) :1590-1611
[2]   Advances in adult and pediatric asthma [J].
Apter, AJ ;
Szefler, SJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2006, 117 (03) :512-518
[3]   pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease [J].
Beloqui, Ana ;
Coco, Regis ;
Memvanga, Patrick B. ;
Ucakar, Bernard ;
des Rieux, Anne ;
Preat, Veronique .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2014, 473 (1-2) :203-212
[4]   Zn/Ga - DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma [J].
Bibi, Haim ;
Vinokur, Vladimir ;
Waisman, Dan ;
Elenberg, Yigal ;
Landesberg, Amir ;
Faingersh, Anna ;
Yadid, Moran ;
Brod, Vera ;
Pesin, Jimy ;
Berenshtein, Eduard ;
Eliashar, Ron ;
Chevion, Mordechai .
REDOX BIOLOGY, 2014, 2 :814-819
[5]   Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and NOS expression in chronic experimental colitis [J].
Camacho-Barquero, Laura ;
Villegas, Isabel ;
Sanchez-Calvo, Juan Manuel ;
Talero, Elena ;
Sanchez-Fidalgo, Susana ;
Motilva, Virginia ;
de la Lastra, Catalina Alarcon .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2007, 7 (03) :333-342
[6]   Intranasal curcumin attenuates airway remodeling in murine model of chronic asthma [J].
Chauhan, Preeti S. ;
Subhashini ;
Dash, D. ;
Singh, Rashmi .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2014, 21 (01) :63-75
[7]   4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling [J].
Chen, Huang-Hui ;
Chen, Yu-Tsen ;
Huang, Yen-Wen ;
Tsai, Hui-Ju ;
Kuo, Ching-Chuan .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (06) :1054-1066
[8]   Asthma research in China: A five-year review [J].
Chen, Zhi-Hua ;
Wang, Ping-Li ;
Shen, Hua-Hao .
RESPIROLOGY, 2013, 18 :10-19
[9]   Protective Effect of Curcumin on Acute Airway Inflammation of Allergic Asthma in Mice Through Notch1-GATA3 Signaling Pathway [J].
Chong, Lei ;
Zhang, Weixi ;
Nie, Ying ;
Yu, Gang ;
Liu, Liu ;
Lin, Li ;
Wen, Shunhang ;
Zhu, Lili ;
Li, Changchong .
INFLAMMATION, 2014, 37 (05) :1476-1485
[10]   Long-term effect of curcumin down-regulates expression of tumor necrosis factor-α and interleukin-6 via modulation of E26 transformation-specific protein and nuclear factor-κB transcription factors in livers of lymphoma bearing mice [J].
Das, Laxmidhar ;
Vinayak, Manjula .
LEUKEMIA & LYMPHOMA, 2014, 55 (11) :2627-2636