RT Journal Article
SR Electronic
T1 Nociceptin orphanin FQ (N/OFQ) – N/OFQ peptide (NOP) receptor system plays a key immunomodulatory role in asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3869
VO 44
IS Suppl 58
A1 Shailendra Singh
A1 Nikol Sullo
A1 Maria Matteis
A1 Giuseppe Spaziano
A1 Konrad Urbanek
A1 Antonella De Angelis
A1 Raffaele De Palma
A1 Ruth Saunders
A1 Lucy Woodman
A1 Bruno D'Agostino
A1 Christopher Brightling
A1 David Lambert
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P3869.abstract
AB 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 ΔCT=11±0.7,n=13), bronchial epithelial cells (mean ΔCT=10±0.49,n=12) and peripheral blood eosinophils (mean ΔCT=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.