25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation

• Published in: PloS one 2014-11, Vol.9 (11), p.e111599-e111599
• Main Authors: Lan, Nan, Luo, Guangyan, Yang, Xiaoqiong, Cheng, Yuanyuan, Zhang, Yun, Wang, Xiaoyun, Wang, Xing, Xie, Tao, Li, Guoping, Liu, Zhigang, Zhong, Nanshan
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D; Active Transport, Cell Nucleus - drug effects; Adrenal Cortex Hormones - pharmacology; Adrenal Cortex Hormones - therapeutic use; Allergies; Asthma; Asthma - drug therapy; Asthma - genetics; Asthma - metabolism; Asthma - physiopathology; Biology and Life Sciences; Biomarkers; Biotechnology; Calcifediol - deficiency; Cell Line; Cell lines; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Chronic obstructive pulmonary disease; Comparative analysis; Corticosteroids; Damage; Deoxyribonucleic acid; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Disease; DNA; DNA Damage; Drug Resistance; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Female; Forced Expiratory Volume - drug effects; Gene expression; Glucocorticoid receptors; Glucocorticoids; Hospitals; Humans; Hydrogen peroxide; Inflammation; Laboratories; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Medicine and Health Sciences; Middle Aged; Monocytes; NF-kappa B - metabolism; NF-κB protein; Nuclear transport; OGG1 protein; Oxidation resistance; Oxidative stress; Oxidative Stress - drug effects; Pathogens; Patients; Phosphorylation; Reactive oxygen species; Receptors; Receptors, Glucocorticoid - metabolism; Respiratory diseases; Respiratory tract; Rodents; Steroids (Organic compounds); Superoxide Dismutase - metabolism; Translocation; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vitamin D; Vitamin D3; Vitamin deficiency
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111599

Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation.