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

Yan Zhou,1,* Yishu Xue,1,* Aihua Bao,1,* Lei Han,1 Wuping Bao,1 Chao Xia,2 Xue Tian,1 Min Zhang1 1Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200081, People’s Republic of China; 2Department of Gerontology, Xin Hua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min ZhangDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of ChinaTel +86 21 63071428Email min.zhang@shgh.cnBackground 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.Keywords: vitamin D, allergic airway inflammation, asthma, autophagy, LC3, Beclin-1, ATG5