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The Role of Nociceptin/Orphanin FQ (N/OFQ) in Inflammation and Remodelling of the Small Airways in a Murine Model of Airway Hyperresponsivness
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A5799 - The Role of Nociceptin/Orphanin FQ (N/OFQ) in Inflammation and Remodelling of the Small Airways in a Murine Model of Airway Hyperresponsivness
Author Block: G. Spaziano1, G. Tartaglione2, M. Sgambato1, T. Russo1, A. Liparulo1, R. Esposito3, S. Sirico1, F. Roviezzo4, L. Gallelli5, B. D'Agostino6; 1Department of Experimental Medicine, University of Campania Luigi vanvitelli, Napoli, Italy, 2Department of Experimental Medicine, University of Campania Luigi vanvitelli, Naples, Italy, 3Department of Experimental Medicine, University of Campania Luigi vanvitelli, CERVINARA, Italy, 4Department of Pharmacy, University of Naples Federico II, Napoli, Italy, 5Department of Experimental Medicine, University of Catanzaro, catanzaro, Italy, 6Department of Experimental Medicine, University of Campania Luigi vanvitelli, NAPLES, Italy.
Rationale: It is now widely recognized that airway inflammation and remodelling take place not only in the central airways but also in the small airways. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). To understand the involvement of N/OFQ in the inflammation and remodelling of the small airways, we used a conventional murine model of AHR. Methods: Balb/c mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. From day 21 to 23, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS. 24 h after the last challenge, animals were sacrificed, and functional evaluations and sample collection were performed. Results: In the animals that received N/OFQ, was observed an important increase of airway compliance (Caw). The analysis of BAL, confirming our previous results, showed that N/OFQ reduce total cell number, reducing eosinophils and lymphocytes. Airway remodelling has been proposed as a mechanism which could explain many clinical features of asthma. The bronchial wall thickness in OVA mice was significantly greater than in the control animals. Instead, N/OFQ treatment showed a significant reduction of the total wall area compared with OVA mice. Morphometric analysis showed that N/OFQ treatment attenuated the hyperplastic phase of airway smooth muscle mass. The changes in these regions were also associated with perturbed alveolar attachments, that were partially restored following treatment with N/OFQ. Conclusion: In conclusion, these results showed the positive effects of N/OFQ on inflammatory process, on the mechanical properties of the small airways and on remodelling of small airways, suggesting a new potential treatment of asthma.
Author Block: G. Spaziano1, G. Tartaglione2, M. Sgambato1, T. Russo1, A. Liparulo1, R. Esposito3, S. Sirico1, F. Roviezzo4, L. Gallelli5, B. D'Agostino6; 1Department of Experimental Medicine, University of Campania Luigi vanvitelli, Napoli, Italy, 2Department of Experimental Medicine, University of Campania Luigi vanvitelli, Naples, Italy, 3Department of Experimental Medicine, University of Campania Luigi vanvitelli, CERVINARA, Italy, 4Department of Pharmacy, University of Naples Federico II, Napoli, Italy, 5Department of Experimental Medicine, University of Catanzaro, catanzaro, Italy, 6Department of Experimental Medicine, University of Campania Luigi vanvitelli, NAPLES, Italy.
Rationale: It is now widely recognized that airway inflammation and remodelling take place not only in the central airways but also in the small airways. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). To understand the involvement of N/OFQ in the inflammation and remodelling of the small airways, we used a conventional murine model of AHR. Methods: Balb/c mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. From day 21 to 23, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS. 24 h after the last challenge, animals were sacrificed, and functional evaluations and sample collection were performed. Results: In the animals that received N/OFQ, was observed an important increase of airway compliance (Caw). The analysis of BAL, confirming our previous results, showed that N/OFQ reduce total cell number, reducing eosinophils and lymphocytes. Airway remodelling has been proposed as a mechanism which could explain many clinical features of asthma. The bronchial wall thickness in OVA mice was significantly greater than in the control animals. Instead, N/OFQ treatment showed a significant reduction of the total wall area compared with OVA mice. Morphometric analysis showed that N/OFQ treatment attenuated the hyperplastic phase of airway smooth muscle mass. The changes in these regions were also associated with perturbed alveolar attachments, that were partially restored following treatment with N/OFQ. Conclusion: In conclusion, these results showed the positive effects of N/OFQ on inflammatory process, on the mechanical properties of the small airways and on remodelling of small airways, suggesting a new potential treatment of asthma.
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