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.

Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness

“…Indeed, to support the immunomodulatory effect of the N/OFQ in a Th2 environment, we evaluated the pulmonary reactivity of N/OFQ‐treated CD1 mice vs. BALB/c. N/OFQ system was able to modulate lung reactivity of Th2‐prone BALB/c mice compared to the Th1‐prone mouse strain CD1 . Indeed, we did not obtain the same results in CD1 mice as those observed in BALB/c mice on pulmonary resistances, indicating the ability of N/OFQ to modulate AHR, a key aspect of the asthmatic disease only in a Th2‐like environment.…”

Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

“…Animals were injected with 0.4 ml s.c. of a suspension containing 100 μg of OVA absorbed to 3.3 mg of aluminium hydroxide gel on days 1 and 8 (OVA-sensitized mice) ( Figure 1A ) (Das et al, 1997; Roviezzo et al, 2007, 2015; Sullo et al, 2013). Salvinorin A (10 mg/kg; Rossi et al, 2016) or vehicle (dimethyl sulfoxide 4%, 0.5 ml) were administered i.p.…”

New Role of Adult Lung c-kit+Cells in a Mouse Model of Airway Hyperresponsiveness

“…As previously described, water-jacketed perspex chamber (water temperature, 37°C) was used to accommodate surgery, perfusion, and ventilation [29]. In anesthetized mouse, the trachea was exposed and cannulated.…”