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Clin Exp Allergy ; 43(6): 672-83, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23711130

RESUMO

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.


Assuntos
Suplementos Nutricionais , Inflamação/metabolismo , Hipersensibilidade Respiratória/metabolismo , Vitamina D/metabolismo , Remodelação das Vias Aéreas/efeitos dos fármacos , Remodelação das Vias Aéreas/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Quimiocinas/biossíntese , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Ovalbumina/imunologia , Hipersensibilidade Respiratória/imunologia , Fator de Transcrição RelA/metabolismo , Vitamina D/administração & dosagem , alfa Carioferinas/metabolismo
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