Source: International Congress 2014 – New mechanisms in the pathogenesis of asthma and other lung diseases
Disease area: Airway diseases

Abstract

Asthma is characterised by airflow obstruction, airway hyper-responsiveness and airway inflammation. The heptadecapeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide (NOP) receptor, a non-opioid member of the opioid receptor family. Role of N/OFQ-NOP system in asthma is uncertain. We sought to evaluate N/OFQ-NOP expression in human airway tissues and relate this to an established animal model of asthma.NOP expression was investigated by qRT-PCR. Its functional role was then interrogated using a range of assays including migration, collagen gel contraction and wound healing. We further investigated the functional role of N/OFQ in vivo using ovalbumin-sensitised mice.NOP expression was detected in human airway smooth muscle cells (mean DCT=11±0.7,n=13), bronchial epithelial cells (mean DCT=10±0.49,n=12) and peripheral blood eosinophils (mean DCT=10.4±1.2,n=16). N/OFQ inhibited chemoattractant-induced migration of eosinophils (p<0.01). N/OFQ stimulated significant HBEC wound closure with 49.62±3.58 % (p<0.001,n=8) of the wound area healed relative to the control (30.88±4.13 %, n=8) 18 h post-wound. Similarly N/OFQ significantly promoted HASM wound closure (p<0.01). Pre-treatment with N/OFQ significantly reduced agonist-induced airway hyper-responsiveness using in vitro (p<0.01) and in vivo models (p<0.001). Ex vivo animal studies showed that N/OFQ significantly inhibits release of inflammatory mediators, mucus hyper-secretion and eosinophil infiltration within the airways.This study provides a comprehensive and complementary in vivo and in vitro evidence for a role of NOP activation in the pathogenesis of asthma.

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S. Singh, N. Sullo, M. Matteis, G. Spaziano, K. Urbanek, A. De Angelis, R. De Palma, R. Saunders, L. Woodman, B. D'Agostino, C. Brightling, D. Lambert (Leicester, United Kingdom; Naples, Italy). Nociceptin orphanin FQ (N/OFQ) – N/OFQ peptide (NOP) receptor system plays a key immunomodulatory role in asthma. Eur Respir J 2014; 44: Suppl. 58, 3869

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