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Keywords:

  • allergic airway in?ammation;
  • asthma;
  • importin-α3;
  • NF-κB;
  • T-regulatory cells;
  • vitamin D;
  • vitamin D receptor

Summary

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.

Conclusion and Clinical Relevance

Vitamin D could be beneficial as an adjunct therapy in the treatment of allergic asthma.