Gorman Shelley, Buckley Alysia G, Ling Kak-Ming, Berry Luke J, Fear Vanessa S, Stick Stephen M, Larcombe Alexander N, Kicic Anthony, Hart Prue H
Telethon Kids Institute University of Western Australia, Subiaco, Western Australia, Australia
Centre of Microscopy, Characterisation and Analysis The University of Western Australia, Nedlands, Western Australia, Australia.
Physiol Rep. 2017 Aug;5(15). doi: 10.14814/phy2.13371.
In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset. Female BALB/c dams were fed a vitamin D-supplemented (2280 IU/kg, VitD) or nonsupplemented (0 IU/kg, VitD) diet from 3 weeks of age, and mated at 8 weeks of age. Male offspring were fed the same diet as their mother. Some offspring initially fed the VitD diet were switched to a VitD diet from 8 weeks of age (VitD). At 12 weeks of age, signs of low-level inflammation were observed in the bronchoalveolar lavage fluid (BALF) of VitD mice (more macrophages and neutrophils), which were suppressed by subsequent supplementation with vitamin D There was no difference in the level of expression of the tight junction proteins occludin or claudin-1 in lung epithelial cells of VitD mice compared to VitD mice; however, claudin-1 levels were reduced when initially vitamin D-deficient mice were fed the vitamin D-containing diet (VitD). Reduced total IgM levels were detected in BALF and serum of VitD mice compared to VitD mice. Lung mRNA levels of the vitamin D receptor (VDR) were greatest in VitD mice. Total IgG levels in BALF were greater in mice fed the vitamin D-containing diet, which may be explained by increased activation of B cells in airway-draining lymph nodes. These findings suggest that supplementation of initially vitamin D-deficient mice with vitamin D suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs.
在疾病状态下，维生素D对于维持最佳的肺上皮完整性和抑制炎症可能很重要，但在疾病发作前其作用尚鲜为人知。雌性BALB/c母鼠从3周龄开始喂食补充维生素D（2280国际单位/千克，VitD）或未补充维生素D（0国际单位/千克，VitD）的饮食，并在8周龄时交配。雄性后代喂食与母亲相同的饮食。一些最初喂食VitD饮食的后代从8周龄开始改为VitD饮食（VitD）。在12周龄时，在VitD小鼠的支气管肺泡灌洗液（BALF）中观察到低水平炎症迹象（更多巨噬细胞和中性粒细胞），随后补充维生素D可抑制这些迹象。与VitD小鼠相比，VitD小鼠肺上皮细胞中紧密连接蛋白occludin或claudin-1的表达水平没有差异；然而，当最初维生素D缺乏的小鼠喂食含维生素D的饮食（VitD）时，claudin-1水平降低。与VitD小鼠相比，在VitD小鼠的BALF和血清中检测到总IgM水平降低。维生素D受体（VDR）的肺mRNA水平在VitD小鼠中最高。喂食含维生素D饮食的小鼠BALF中的总IgG水平更高，这可能是由于引流气道淋巴结中B细胞的激活增加所致。这些发现表明，给最初维生素D缺乏的小鼠补充维生素D可抑制肺部炎症迹象，但对肺上皮完整性的影响有限。
