Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse

PCLS were used to analyze ex-vivo effects of beclomethasone on inhibiting bronchoconstriction in the horse. The inhibiting effect was measured through instillation of a known mediator of inflammation and bronchoconstriction, leukotriene C4. For this, the accessory lobes of 13 horses subjected to euthanasia for reasons unrelated to the respiratory apparatus were used to obtain viable lung slices.After 30？minutes of PCLS incubation, beclomethasone showed to significantly inhibit the contraction of the bronchioles after instillation with leukotriene C4. The EC50 values of the two contraction curves (LTC4 with and without BDP) differed significantly from each other (p？=？0.002). The possibility of a non-genomic rapid mechanism of action seems likely since transcriptional activities require a longer lag period.In human neuroendocrinology, high levels of glucocorticoids have been proven to function via a non-genomic mechanism of membrane receptors. The concentration of beclomethasone used on the lung slices in our study can be considered as high. This allows speculation about similar rapid non-genomic mechanisms of high-dosage inhaled glucocorticoids in the lower airways of horses. However, further assessment on a molecular basis is needed to confirm this.The exact interactions of the single inflammatory mediators within the inflammatory cascade taking place during recurrent airway obstruction (RAO) in the horse are still unclear. Ex-vivo precision-cut lung slices (PCLS) from terminal airways of the horse offer a unique condition where the interaction of single inflammatory agents (i.e. bronchoconstrictors) and anti-inflammatory agents (i.e. bronchodilators) can be observed without multifactorial influence as occurs in vivo. This may be useful to further understand the pathogenesis of RAO. The aim of the study was to take a first step to analyse the interaction of two substances involved in bronchoconstriction and bronchodilation in healthy pulmonary tissue of 13 horses.Sy