title: Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.
abstract: Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, United States of America.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Fischer
authors.affiliation: Department of Biomedical Science, Creighton University School of Medicine, Omaha, NE, United States of America.
authors.forename: Sannette C
authors.initials: SC
authors.lastname: Hall
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, United States of America.|Department of Biomedical Science, Creighton University School of Medicine, Omaha, NE, United States of America.|Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States of America.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015820:Cadherins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D014746:Vimentin / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D000485:Allergens; D015820:Cadherins; D016207:Cytokines; D014746:Vimentin; D014807:Vitamin D; D007073:Immunoglobulin E