title: Vitamin D supplementation reduces airway hyperresponsiveness and allergic airway inflammation in a murine model.
abstract: BACKGROUND
  Asthma is a chronic disease associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodelling. NF-κB is a transcriptional factor that regulates and co-ordinates the expression of various inflammatory genes. The NF-κB subunits, p50 and Rel-A, are translocated to the nucleus by importin α3 and importin α4. There is growing evidence that vitamin D is a potent immunomodulator. However, the evidence for beneficial or adverse effects of vitamin D in asthma is still unclear.
  
  
  OBJECTIVE
  In this study, we examined the effect of vitamin D status on AHR, airway inflammation and cytokines in the bronchoalveolar lavage fluid (BALF) in a murine model of allergic asthma.
  
  
  METHODS
  Female BALB/c mice were fed with special vitamin D-deficient or vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet for 13 weeks. Mice were sensitized and challenged with ovalbumin (OVA). The effect of vitamin D on lung histology, AHR, T regulatory cells (Tregs) and BALF cytokines was examined. The expression of importin-α3 and Rel-A in the lung of OVA-sensitized mice was analysed using immunofluorescence.
  
  
  RESULTS
  Vitamin D deficiency was associated with higher AHR in OVA-sensitized and challenged mice than those in vitamin D-sufficient mice. This was accompanied with marked signs of airway remodelling, high BALF eosinophilia, increased BALF pro-inflammatory cytokines, reduced BALF IL-10 levels, reduced blood Tregs, increased expression of importin-α3 and Rel-A in the lung tissue. Vitamin D supplementation attenuated the pro-inflammatory effects, but did not completely reverse the features of allergic airway inflammation.
  
  
  CONCLUSIONS
  Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.
authors.affiliation: Department of Biomedical Sciences and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: T
authors.initials: T
authors.lastname: Agrawal
authors.forename: G K
authors.initials: GK
authors.lastname: Gupta
authors.forename: D K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014807:Vitamin D / Q000008:administration & dosage / Q000378:metabolism*; D028901:alpha Karyopherins / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D051996:Transcription Factor RelA; D028901:alpha Karyopherins; C523975:importin alpha 3, mouse; D014807:Vitamin D; D010047:Ovalbumin