Abstract
BackgroundParticulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.ObjectivesMechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.MethodsTranscriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.ResultsTranscriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.ConclusionsIn a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.
Highlights
Asthma is the most common chronic lung disease with globally increasing prevalence, implying the importance of environmental factors in its aetiology [1]
Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary human bronchial epithelial cells (HBECs) from healthy and asthmatic donors cultured with reference urban Particulate matter (PM) in the presence/absence of vitamin D
In the urban environment Rosser and colleagues have shown that vitamin D insufficient children, but not those vitamin D sufficient, living close to major roads show an elevated risk of severe asthma exacerbations [12], the mechanisms by which vitamin D may protect against pollution toxicity remain unclear and the interaction likely complex
Summary
Asthma is the most common chronic lung disease with globally increasing prevalence, implying the importance of environmental factors in its aetiology [1]. Vitamin D insufficiency/deficiency and ambient air pollution are two major environmental factors that appear to influence the pathogenesis and stability of asthma [2] [3] [4] [5], as well as other respiratory diseases [6] [7]. European studies have shown heterogeneity between different cities in the magnitude of the effects of pollution on health outcomes such as hospital admissions for respiratory diseases [9] and asthma incidence [11], despite using standardised analyses. In the urban environment Rosser and colleagues have shown that vitamin D insufficient children, but not those vitamin D sufficient, living close to major roads show an elevated risk of severe asthma exacerbations [12], the mechanisms by which vitamin D may protect against pollution toxicity remain unclear and the interaction likely complex. Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma
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