Modulation of airway epithelial cell function by vitamin D in COPD

Vitamin D plays an active role in the modulation of innate and adaptive immune responses as well as in the protection against respiratory pathogens, e.g. by increasing expression of the antimicrobial peptide hCAP18/LL-37. The main aim of this thesis was to elucidate the role of inflammation on the protective effects of vitamin D on respiratory host defense responses in chronic inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD). Airway epithelial host defense responses in COPD patients are defective and these patients are therefore more susceptible to respiratory infections. In this thesis we have shown that exposure to cigarette smoke, a main risk factor for COPD, reduced expression of certain host defense mediators by affecting end-stage airway epithelial differentiation and might explains why COPD patients are more susceptible to respiratory infections. We have further demonstrated in the studies presented in this thesis that certain airway inflammatory mediators could possibly interfere with vitamin D metabolism by promoting expression of vitamin D degrading enzyme CYP24A1, thereby reducing local levels of vitamin D and accompanying protective antimicrobial and anti-inflammatory actions. These new insights may yield possible new strategies to target CYP24A1 that enhance local levels and signaling of vitamin D to increase protection against exacerbations in COPD patients. The research of this thesis was financially supported by the Lung Foundation Netherlands (project code: 5.1.13.033). The printing of this thesis was financially supported by: Lung Foundation Netherlands and Stichting Astma Bestrijding.LUMC / Geneeskund

P63+Krt5+basal cells are increased in the squamous metaplastic epithelium of patients with radiation-induced chronic Rhinosinusitis

10.1186/s13014-020-01656-7Radiation Oncology15122