25-Hydroxyvitamin D3-Deficiency Enhances Oxidative Stress and Corticosteroid Resistance in Severe Asthma Exacerbation

Abstract

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.

The R213G polymorphism in SOD3 protects against allergic airway inflammation

“…(42)(43)(44)(45)(46)(47). Allergic asthma, oxidative stress, and lung inflammation go hand-in-hand (48,49). There are reports suggesting that EC-SOD plays a major role in determining the progression of allergic lung disease by controlling DC maturation and T lymphocyte priming, differentiation, proliferation, and activation (25).…”

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“…Long-term follow-up of these patients is eagerly awaited. Liu et al 2006-Handsottir et al 2010-Beard et al 2011-Fabri et al 2011-Ruiter et al 2015-Ethier et al 2016 M A N U S C R I P T A C C E P T E D Liu et al 2006-Fabri et al 2011-Lan et al 2014-Xystrakis et al 2006-Nanzer et al 2014-Chambers et al 2015 reduced pro-inflammatory cytokine production by neutrophils but with enhanced anti-bacterial activity -Takahashi et al 2002-Subramanian et al 2017 …”

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“…However, Vit D does not affect GR phosphorylation at S211 [47]. Patients with severe asthma exacerbation with Vit D deficiency showed oxidative stress and DNA damage in peripheral blood monocytes [48].…”