S20 CRTH2 is expressed by the bronchial epithelium and its activation drives epithelial differentiation

Abstract

healed relative to the control (30.88 ± 4.13%, n = 8)18 h postwound. Similarly N/OFQ significantly promoted HASM wound closure (p < 0.01). Our findings showed that SCF-stimulated IL-8 release (4.43 ± 0.69 fold over control, p < 0.01,n = 7) was significantly inhibited by N/OFQ (3.32 ± 0.56 fold over control, p < 0.01, n = 7). Ex vivo human studies demonstrate significantly (p < 0.01) increased endogenous N/OFQ in asthmatic airways relative (sputum N/OFQ:59.02 ± 2.57 pg/ml,n = 26) to healthy airways (sputum N/OFQ:44.69 ± 0.43,n = 10) and identifies eosinophils as a potential source for these. Pre-treatment with N/OFQ was shown to significantly reduce agonistinduced bronchial hyper-responsiveness using in vitro (p < 0.01) and in vivo models (p < 0.001). Ex vivo animal studies show that N/OFQ significantly inhibits release of inflammatory mediators including IL4, IL5, IL12, IL13 and inflammatory cell recruitment including mast cells and eosinophils within the airways. Further mucus hyper-secretion was also reduced following N/OFQ pre-treatment in these models. This is the first study to perform a comprehensive and complementary in vivo and in vitro study of the expression and actions of the N/OFQ-NOP system in the airways and provide evidence for a role of NOP activation in the management of asthma.