Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter

Abstract

41 Background: Particulate matter (PM) pollutant exposure, which induces oxidative stress and 42 inflammation, and vitamin D insufficiency, which compromises immune regulation, are 43 detrimental in asthma. 55 versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-56 CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D 57 increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of 58 reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-59 isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 60 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, 61 supporting a role for this pathway in the anti-inflammatory actions of vitamin D. 62 Conclusions: In a study using HBECs from 18 donors, vitamin D enhanced HBEC 63 antioxidant responses and modulated the immune response to PM, suggesting that vitamin D 64 may protect the airways from pathological pollution-induced inflammation. prevalence, implying the importance of environmental factors in its aetiology [1]. Vitamin D 68 insufficiency/deficiency and ambient air pollution are two major environmental factors that 69 appear to influence the pathogenesis and stability of asthma [2] [3] [4] [5], as well as other 70 respiratory diseases [6] [7]. However there remains debate resulting from the heterogeneity 71 of findings relating to the effects of these environmental factors on airway pathology [5] [8] [9] 72 [10]. For example, European studies have shown heterogeneity between different cities in 73 the magnitude of the effects of pollution on health outcomes such as hospital admissions for 74 respiratory diseases [9] and asthma incidence [11], despite using standardised analyses. 75 Environment-environment interactions are a major possible explanation for inconsistent 76 results between different patient cohorts but have been little studied, particularly at the 77 mechanistic level. In a recent meta-analysis, latitude of study location influenced 78 associations between air pollutants and severe asthma exacerbations, and latitude is also 79 known to affect sunlight-derived vitamin D production, although this association is 80 complicated by other factors such as hours of daily skin exposure to sunlight [5]. In the 81 urban environment Rosser and colleagues have shown that vitamin D insufficient children, 82 but not those vitamin D sufficient, living close to major roads show an elevated risk of severe 83 asthma exacerbations [12], although the mechanisms by which vitamin D may protect 84 against pollution toxicity remain unclear and the interaction likely complex. 85 86 A growing body of research highlights the importance of epithelial immunology in 87 asthma [13]. Evidence shows that inhaled ambient particulate matter (PM) adversely affects 88 the bronchial epithelium through various mechanisms including the imposition of oxidative 89 stress, which stimulates redox sensi...

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