Effect of Vitamin D Deficiency and Supplementation in Lactation and Early Life on Allergic Airway Inflammation and the Expression of Autophagy-Related Genes in an Ovalbumin Mouse Model.
Effect of Vitamin D Deficiency and Supplementation in Lactation and Early Life on Allergic Airway Inflammation and the Expression of Autophagy-Related Genes in an Ovalbumin Mouse Model.
复制标题
哺乳期和生命早期维生素 D 缺乏和补充对卵清蛋白小鼠模型过敏性气道炎症和自噬相关基因表达的影响
DOI：
10.2147/jir.s321642
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发表时间：
2021
影响因子：
4.5
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Zhou Y;Xue Y;Bao A;Han L;Bao W;Xia C;Tian X;Zhang M
维生素D参与多种生理和病理过程，包括炎症和自噬。我们旨在研究哺乳期及生命早期开始的饮食中维生素D缺乏或补充，对卵清蛋白（OVA）小鼠模型炎症和自噬的影响。
雌性BALB/c小鼠在整个哺乳期分别喂食维生素D缺乏、充足或补充的饮食，其后代断奶后遵循相同饮食。随后，对后代小鼠用OVA进行致敏和激发，测量气道阻力（RL），并收集其血清、支气管肺泡灌洗液（BALF）和肺组织。从肺组织中分离肺泡巨噬细胞（AMs），并用不同浓度的1,25-二羟基维生素D3 [1,25(OH)₂D₃] 进行培养。检测肺组织和AMs中自噬相关（ATG）蛋白，包括轻链3（LC3）、Beclin - 1和ATG5，以及核因子κB p65（NF - κB p65）的表达。
与维生素D充足组或补充组相比，OVA致敏和激发在维生素D缺乏组诱发了更为显著的过敏性气道炎症和更高的气道阻力。与维生素D补充的OVA介导组相比，维生素D缺乏的OVA介导组肺组织中包括LC3、Beclin - 1和ATG5在内的ATG蛋白以及NF - κB p65的表达增加。LC3 mRNA的表达与BALF中炎症细胞数量和细胞因子之间存在相关性。在体外，1,25(OH)₂D₃也以时间和剂量依赖的方式调节AMs中LC3、Beclin - 1、ATG5和NF - κB p65 mRNA的表达。
生命早期维生素D缺乏可能会加重过敏性气道炎症，生命早期维持充足的维生素D对肺部健康至关重要。维生素D可能调节OVA致敏/激发小鼠肺部的自噬，从而在OVA诱导的过敏性气道炎症中发挥保护作用。
Background and Objective Vitamin D is involved in various physiological and pathological processes, including inflammation and autophagy. We aimed to investigate the effects of dietary vitamin D deficiency or supplementation initiated in lactation and early life on inflammation and autophagy in an ovalbumin (OVA) mouse model. Methods Female BALB/c were fed with vitamin D-deficient, sufficient or supplemented diets throughout lactation and their offspring followed the same diet after weaning. Offspring were then sensitized and challenged with OVA, airway resistance (RL) was measured, and their serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected. Alveolar macrophages (AMs) were isolated from lung tissue and cultured with different concentrations of 1,25(OH)2D3. The expressions of autophagy-related (ATG) proteins including light-chain 3 (LC3), Beclin-1, and ATG5, and NF-κB p65 in lung tissue and AMs were measured. Results OVA sensitization and challenge induced dramatic allergic airway inflammation and higher RL in the vitamin D-deficient group compared with vitamin D-sufficient or the supplemented group. The expression of ATGs including LC3, Beclin-1, and ATG5, and NF-κB p65 in lung tissue in the vitamin D-deficient OVA-mediated group was increased compared with vitamin D-supplemented OVA-mediated group. There was correlation between the expression of LC3 mRNA and inflammatory cell numbers and cytokines in BALF. In vitro, 1,25(OH)2D3 also regulated the expression of LC3, Beclin-1, ATG5, and NF-κB p65 mRNA in AMs in a time- and dose-dependent manner. Conclusion Deficiency of vitamin D in early life may aggravate allergic airway inflammation, and maintaining sufficient vitamin D during early life is necessary for lung health. Vitamin D may modulate autophagy in lungs of OVA sensitized/challenged mice, thus playing a protective role in OVA-induced allergic airway inflammation.