25-Hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation.
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.
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Nan
N
Lan
Hygiene Section, Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Guangyan
G
Luo
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Xiaoqiong
X
Yang
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Yuanyuan
Y
Cheng
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Yun
Y
Zhang
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Xiaoyun
X
Wang
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Xing
X
Wang
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China.
Tao
T
Xie
Inflammations & Allergic Diseases Research Unit, Affiliated Hospital of Luzhou Medical College, Luzhou, 646000, Sichuan, China; State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, Guangdong, 518060, PR China.
Guoping
G
Li
State Key Laboratory of Respiratory Disease for Allergy at Shengzhen University, School of Medicine, Shenzhen University, Nanhai Ave 3688, Shenzhen, Guangdong, 518060, PR China.
Zhigang
Z
Liu
State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangdong, 510120, PR China.
Nanshan
N
Zhong
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002112:Calcifediol / Q000172:deficiency*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D013482:Superoxide Dismutase; D002112:Calcifediol