Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model
Celastrol suppresses allergen-induced airway inflammation in a mouse allergic asthma model
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DOI：
10.1016/j.ejphar.2009.03.078
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发表时间：
2009-06-10
影响因子：
5
通讯作者：
Ro, Jai Youl
中科院分区：
文献类型：
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作者：
Kim, Dae Yong;Park, Jung Won;Ro, Jai Youl
雷公藤红素具有抗炎和免疫调节作用。但它的抗过敏作用仍然知之甚少。因此，我们旨在研究celastrol对小鼠变应性哮喘模型哮喘反应的抑制能力。对BALB/c小鼠进行致敏和卵清蛋白刺激诱导哮喘。我们分别用diff - quick染色、苏木精染色和伊红染色测量了炎症细胞向支气管肺泡灌洗液或肺组织的募集，用周期性酸-希夫（PAS）染色测量了杯状细胞增生，用Flexvent系统测量了气道的高反应性。采用逆转录酶聚合酶链反应和酶联免疫吸附法分别检测细胞因子、基质金属蛋白酶（MMPs）和组织金属蛋白酶抑制剂（TIMPs） mRNA和蛋白的表达，采用Western blot和电泳迁移位移法分别检测支气管肺泡灌洗细胞和肺组织中丝裂原活化蛋白（MAP）激酶和核因子κ B （nf - κ B）的活性。雷公藤红素可减少支气管肺泡灌洗液和支气管周围区域炎症细胞总数，降低气道高反应性，降低炎性细胞因子IL -4、IL-13、tnf - α和ifn - γ mRNA和蛋白表达水平。对于MMPs和TIMPs，在卵清蛋白诱导的小鼠过敏性哮喘中，支气管肺泡灌洗细胞和肺组织中MAP激酶和nf - κ B活性升高。我们的数据表明，口服雷公藤红素通过炎症细胞中MAP激酶/ nf - κ B调节炎症细胞因子MMP-2/-9和TIMP-1/-2的失衡，从而抑制卵白蛋白诱导的气道炎症、高反应性和组织重塑。基于我们的研究结果，我们建议将雷公藤红素用作过敏性哮喘的治疗剂。(C) 2009 Elsevier B.V.版权所有
Celastrol has anti-inflammatory and immunomodulatory activities. but its anti-allergic effects remain poorly understood. Therefore, we aimed to investigate the ability of celastrol to inhibit asthmatic reactions in a mouse allergic asthma model. BALB/c mice were sensitized and challenged with ovalbumin to induce asthma. We measured the recruitment of inflammatory cells into the bronchoalveolar lavage fluid or lung tissues by Diff-Quik and hematoxylin and eosin staining, respectively, goblet cell hyperplasia by periodic acid-Schiff (PAS) staining, airway hyperresponsiveness by Flexvent system. mRNA and protein expression of cytokines, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) by reverse transcriptase polymerase chain reaction and ELISA, respectively, and the activities of mitogen-activated protein (MAP) kinases and nuclear factor-kappa B (NF-kappa B) in the bronchoalveolar lavage cells and lung tissues by Western blot and electrophoretic mobility shift assay (EMSA), respectively. Celastrol reduced the total number of inflammatory cells in the bronchoalveolar lavage fluid and in peribronchial areas, and decreased the airway hyperresponsiveness, mRNA and protein expression levels for inflammatory cytokines such as interieukin (IL)-4, IL-13, TNF-alpha and IFN-gamma. and for MMPs and TIMPs, MAP kinases and NF-kappa B activities in the bronchoalveolar lavage cells and in the lung tissues increased in ovalbumin-induced allergic asthma in mice. Our data suggest that oral administration of celastrol suppresses ovalbumin-induced airway inflammation, hyperresponsiveness, and tissue remodeling by regulating the imbalance of MMP-2/-9 and TIMP-1/-2 by inflammatory cytokines via MAP kinases/NF-kappa B in inflammatory cells. Based on our findings, we suggest that celastrol may be used as a therapeutic agent for allergy-induced asthma. (C) 2009 Elsevier B.V. All rights reserved.