Effects of vitamin D on inflammation and oxidative stress in airway epithelial cells

Norton, Rosemary (2012) Effects of vitamin D on inflammation and oxidative stress in airway epithelial cells. Doctoral thesis, University of East Anglia.

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Chronic obstructive pulmonary disease (COPD) is a multifactorial and systemic disease driven by inflammation and oxidative stress, predominantly caused by smoking, but exacerbated by infection and pollution. Current therapies aim to treat specific aspects of the disease and/or symptoms rather than the disease as a whole.
Vitamin D, more commonly known for its importance in calcium and phosphorus homeostasis, has now been established as an important immunomodulatory agent. Recent studies have shown vitamin D deficiency to be associated with reduced lung function and COPD disease severity. Equally vitamin D has been shown to modulate a number of inflammatory mediators which are important in COPD pathology. Together, these suggest that vitamin D may be beneficial in COPD. Airway epithelial cells play a central role in COPD pathogenesis and have been shown to constitutively activate vitamin D. This study investigated the effects of vitamin D on inflammation and oxidative stress in human airway epithelial cells, crucially on mediators important in COPD pathology and also investigated the potential mechanisms involved in the action of vitamin D.
Three different human airway epithelial cell lines A549, NCI-H292, 16HBE14o- and primary human small airway epithelial cells were shown to express similar inflammatory mediators, with the 16HBE14o- cells shown to be a useful model of primary cells. Vitamin D significantly modulated IL-6 mRNA and protein expression in the primary cells and reduced MUC5AC mRNA and protein expression in the mucous producing NCI-H292 cells. Interestingly, vitamin D treatment gave a biphasic effect on induction of inflammatory mediators by TNFα in the NCI-H292 cells. Vitamin D also modulated the induction of oxidative stress, antioxidant gene expression and Nrf2 protein expression in the NCI-H292 cells.
This data emphasises the complexity of vitamin D modulation of inflammatory mediators and oxidative stress in airway epithelial cells and provides new novel avenues of future study.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Zoe White
Date Deposited: 07 Feb 2014 10:31
Last Modified: 07 Feb 2014 10:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/41410

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