Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model.

Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model.
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DOI:
10.1111/cea.12102
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发表时间:
2013-06
期刊:
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子:
--
通讯作者:
Agrawal DK
Agrawal DK
中科院分区:
其他
文献类型:
--
作者:
Agrawal T;Gupta GK;Agrawal DK

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哮喘是一种与气道高反应性(AHR)、气道阻塞和气道重塑相关的慢性疾病。NF-κB是一种转录因子,调节和协调各种炎症基因的表达。NF-κB亚基p50和Rel-A通过输入素α3和输入素α4转运至细胞核。越来越多的证据表明维生素D是一种有效的免疫调节剂。然而,维生素D对哮喘有益或有害的证据仍不清楚。在这项研究中,我们研究了维生素D状态对过敏性哮喘小鼠模型的AHR、气道炎症和支气管肺泡灌洗液(BALF)中细胞因子的影响。雌性BALB/c小鼠用特殊的维生素D缺乏或维生素D充足(2,000 IU/kg)或维生素D补充(10,000 IU/kg)饲料喂养13周。致敏小鼠,用卵清蛋白激发。检测维生素D对肺组织学、AHR、T调节细胞和BALF细胞因子的影响。免疫荧光法检测OVA致敏小鼠肺组织中importin-α3和Rel-A的表达。与维生素D充足的小鼠相比,维生素D缺乏与OVA致敏和激发小鼠的AHR较高相关。同时伴有气道重塑、BALF嗜酸性粒细胞增多、BALF促炎细胞因子升高、BALF IL-10水平降低、血T调节细胞减少、肺组织importin-α3和Rel-A表达增加。补充维生素D减弱了促炎作用,但不能完全逆转过敏性气道炎症的特征。维生素D作为过敏性哮喘的辅助治疗可能是有益的。
Asthma is a chronic disease associated with airway hyperresponsiveness (AHR), airway obstruction, and airway remodeling. NF-κB is a transcriptional factor that regulates and co-ordinates the expression of various inflammatory genes. The NF-κB subunits, p50 and Rel-A, are translocated to the nucleus by importin α3 and importin α4. There is growing evidence that vitamin D is a potent immunomodulator. However, the evidence for beneficial or adverse effects of vitamin D in asthma is still unclear. In this study, we examined the effect of vitamin D status on AHR, airway inflammation, and cytokines in the bronchoalveolar lavage fluid (BALF) in a murine model of allergic asthma. Female BALB/c mice were fed with special vitamin D-deficient or vitamin D-sufficient (2,000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet for 13 weeks. Mice were sensitized and challenged with ovalbumin. The effect of vitamin D on lung histology, AHR, T-regulatory cells and BALF cytokines was examined. The expression of importin-α3 and Rel-A in the lung of OVA-sensitized mice was analyzed using immunofluorescence. Vitamin D deficiency was associated with higher AHR in OVA-sensitized and challenged mice than those in vitamin D-sufficient mice. This was accompanied with marked signs of airway remodeling, high BALF eosinophilia, increased BALF pro-inflammatory cytokines, reduced BALF IL-10 levels, reduced blood T-regulatory cells, increased expression of importin-α3 and Rel-A in the lung tissue. Vitamin D supplementation attenuated the pro-inflammatory effects, but did not completely reverse the features of allergic airway inflammation. Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.
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