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

Pfeffer, P. E.; Lu, H.; Mann, E. H.; Chen, Y. H.; Ho, T.-R.; Cousins, D. J.; Corrigan, C.; Kelly, F. J.; Mudway, I. S.; Hawrylowicz, C. M.

doi:10.1101/351791

bioRxiv · 10.1101/351791

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

Pfeffer, P. E.·Lu, H.·Mann, E. H.·Chen, Y. H.·Ho, T.-R.·Cousins, D. J.·Corrigan, C.·Kelly, F. J.·Mudway, I. S.·Hawrylowicz, C. M.

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Abstract

BackgroundParticulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.\n\nObjectivesMechanistic 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.\n\nMethodsTranscriptome 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.\n\nResultsTranscriptome 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.\n\nConclusionsIn 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.

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Pfeffer, P. E., Lu, H., Mann, E. H., Chen, Y. H., Ho, T.-R., Cousins, D. J., Corrigan, C., Kelly, F. J., Mudway, I. S., Hawrylowicz, C. M.. 2018-06-20. Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter.. https://doi.org/10.1101/351791

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