1α,25‐Dihydroxy vitamin D3, the active form of vitamin D3, protects against allergeninduced airway constriction

Abstract

Allergen‐induced bronchoconstriction is an important hallmark of allergic asthma and is caused by the release of mediators, such as histamine, by activated mast cells. In various disease models, the vitamin D3 pathway has been shown to reduce mast cell degranulation. Vitamin D3 is converted into 25‐hydroxy vitamin D3 and subsequently into the active form 1α,25‐dihydroxy vitamin D3 by CYP enzyme activity. Vitamin D3 deficiency contributes to the pathophysiology of allergic diseases, including asthma, whereas vitamin D3 treatment reduces allergen‐induced airway hyperresponsiveness and inflammation in experimental models of asthma.In this study, we investigated the role of the vitamin D3 pathway in regulating allergen‐induced constriction of intrapulmonary airways in an animal model of allergic asthma.To this aim, precision cut lung slices (PCLS) were obtained from guinea pigs that were IgE‐sensitized to ovalbumin (OVA) and sacrificed 4–8 weeks later. Lungs were filled with 1.5% agarose, cooled with ice, harvested and 500‐μm thin PCLS were prepared. Constrictions of the intrapulmonary airways to increasing concentrations of OVA or histamine were monitored using video‐assisted microscopy. PCLS were pre‐treated with or without vitamin D3 compounds 30 minutes prior to the addition of OVA or histamine.OVA induced a dose‐dependent and full constriction of intrapulmonary airways in guinea pig PCLS. Pretreatment with 1α,25‐dihydroxy vitamin D3 (1 μM), the active form of vitamin D3, reduced the sensitivity (pD2) of the airways to OVA by more than 300‐fold (p<0.01), without affecting the maximal constriction (Emax). By contrast, the bronchoconstriction induced by exogenous histamine was not affected by pretreatment with 1α,25‐dihydroxy vitamin D3. Taken together, these findings indicate that the bronchoprotective effect of 1α,25‐dihydroxy vitamin D3 is caused by inhibiting the allergen‐induced release of mast cell mediators rather than by reducing the responsiveness to these mediators.In conclusion, treatment with 1α,25‐dihydroxy vitamin D3 reduces the airway sensitivity towards allergens and subsequent airway constriction, presumably by reducing allergen‐induced mast cell degranulation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.