title: Nociceptin/orphanin FQ receptor activation decreases the airway hyperresponsiveness induced by allergen in sensitized mice.
abstract: Several studies suggest that the N/OFQ (nociceptin/orphanin FQ)-NOP (N/OFQ peptide) receptor pathway is involved in airway physiology. We previously demonstrated a modulation of the endogenous N/OFQ levels in allergen-sensitized mice. Here, we investigated the effects of NOP receptor activation in allergen sensitization using a murine model of allergen-induced airway hyperresponsiveness (AHR). BALB/c mice were intraperitoneally treated with the NOP receptor agonist UFP-112, either during the sensitization phase (30 min before ovalbumin administration) or at the end of sensitization process (15 min before bronchopulmonary reactivity evaluation). At day 21 from the first allergen exposure, bronchopulmonary reactivity and total and differential cell count in bronchoalveolar lavage fluid were evaluated. In a separate set of experiments cell proliferation in lymphocytes, cytokine levels, IgE serum levels, and the effect of UFP-112 on IL-13-induced AHR were evaluated. Pretreatment with UFP-112, during the sensitization phase, caused a significant reduction in allergen-induced AHR and total cell lung infiltration. No effect on allergen-induced AHR was observed when the treatment was performed at the end of sensitization process, on tissues harvested from OVA-sensitized mice and on IL-13-induced AHR. The in vitro proliferative response of lymphocytes was significantly reduced by pretreatment during the sensitization phase with UFP-112. This effect was paralleled by a significant modulation of cytokine secretion in pulmonary tissues and lymphocytes. In conclusion, we demonstrated a role for the NOP receptor and N/OFQ pathway in the AHR induced by allergen, probably through a modulation of the immune response that triggers the development of AHR that involves pro- and anti-inflammatory cytokines.
authors.affiliation: Department of Experimental Medicine-Section of Pharmacology, Faculty of Medicine and Surgery, 2nd University of Naples, 80136 Naples, Italy.
authors.forename: Nikol
authors.initials: N
authors.lastname: Sullo
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Maria
authors.initials: M
authors.lastname: Matteis
authors.forename: Angela
authors.initials: A
authors.lastname: Ianaro
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calò
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Luana
authors.initials: L
authors.lastname: De Gruttola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spaziano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Bruno
authors.initials: B
authors.lastname: D'Agostino
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018847:Opioid Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D011957:Receptors, Opioid / Q000276:immunology* / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D018793:Interleukin-13; D018847:Opioid Peptides; D010047:Ovalbumin; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C525846:nociceptin-amide, Nphe(1)-(pF)Phe(4)-Aib(7)-Arg(14)-Lys(15)-; C000722287:Oprl1 protein, mouse
keywords: airway hyperresponsiveness; allergen sensitization; allergic asthma; immune response; nociceptin/orphanin FQ