Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

Abstract

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 D3‐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 D3. 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 D3‐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 D3‐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 D3 suppresses signs of lung inflammation but has limited effects on the epithelial integrity of the lungs.

Calcium and Cholecalciferol Levels in Late-Phase Laying Hens: Effects on Productive Traits, Egg Quality, Blood Biochemistry, and Immune Responses

“…It is evident that as the metabolism of nutrients decreases with age ( 5 , 41 ), the VD 3 requirements should be reinvestigated in relation to stage of laying considering the impact of aging on VD 3 requirements and due to VD 3 and its metabolites playing a vital role in the uptake, deposition, and excretion of Ca ( 5 , 21 , 42 ). Likewise, other authors ( 5 , 24 , 27 ) showed similar findings. The VD 3 is essential for the formation of Ca-bound proteins, which are involved in the active transport of Ca across the intestine ( 28 ), and in lipoprotein, the precursor of yolk formation ( 5 , 20 , 21 ).…”

“…The Ca-binding protein implicated in the active transport of Ca across the intestinal wall requires VD 3 ( 18 , 22 ). In the literature, VD 3 has many health, immunological, and physiological benefits ( 5 ), and it is a vital vitamin that plays a considerable role in the development of muscle, skeletal health, and in sustaining the homeostasis of calcium and phosphorus ( 18 , 23 , 24 ). Formation of eggshell and health of bone in laying hens is essential and involves the integration between the metabolism of Ca, P, and VD 3 ( 5 , 18 , 25 ).…”

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

“…45 Other studies have proved that, in disease settings, vitamin D has positive effects on maintaining lung epithelial integrity and inhibiting inflammatory responses. 46,47 Vitamin D supplementation ameliorated pulmonary morphological alternations in LPS-induced bronchopulmonary dysplasia, inhibited IFN-γ overproduction and, thereby, suppressed inflammation. 48 Vitamin D was also confirmed to enhance the ability of neutrophils to kill Streptococcus pneumoniae and inhibit excessive inflammation and apoptosis.…”

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism

“…Murine studies that have attempted to address the ability of VD3 supplementation after deficiency have yielded mixed results. While supplementation reduced eosinophil and neutrophil numbers in bronchoalverolar lavage [ 83 ], deficiency correction had only limited effect of improving epithelial integrity in the lung which was only modestly impacted by VD3 deficiency in otherwise healthy mice [ 84 ]. Collectively, these reports and our data highlight the need for additional research into how 25(OH)D3 deficiency and VD3 supplementation regulates local vitamin D metabolism and subsequent airway functions.…”