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.