ABSTRACT
Title
Activation of nociceptin/orphanin FQ receptor inhibits allergen induced airway hyperresponsiveness
Authors
M. Matteis
DoctorateSchool in Pharmacological Sciences and Experimental Medicine
Dept. of Experimental Medicine, Section of Pharmacology – Second University of Naples, Italy
DoctorateSchool in Pharmacological Sciences and Experimental Medicine
Dept. of Experimental Medicine, Section of Pharmacology – Second University of Naples, Italy
Abstract
Airway inflammation, a central component of asthma, may results from a reaction to an inhaled environmental substance that triggers a series of inflammatory events. The N/OFQ and its receptor NOP, a pathway closely related to the opioid system, could have a role in allergen sensitization mechanisms, but its effective involvement in the airway is still unresolved. In our previous study [1], we shown a differential airway responsiveness to capsaicin between naive and ovalbumin that was related to a modulation of the endogenous N/OFQ pathway.
The aim of this study was to investigate, in a conventional murine model of allergen-induced airway hyperresponsiveness (AHR), the role of N/OFQ signalling in the mechanism of allergen sensitization. BALB/c mice were treated intraperitoneally with the NOP receptor agonist UFP-112 or antagonist UFP-101 30 min before ovalbumin systemic sensitization. 21 days later, in vivo and in vitro bronchopulmonary function and lung cell counts were evaluated. In a separate set of experiments, on the 7th day after treatment, cell proliferation assay, cytokine levels and NOP receptor expression were evaluated in lymphocytes and splenocytes. Single administration of the UFP-112 at the time of sensitization significantly reduced AHR both in vivo and in vitro, with an improvement of eosinophylic and lymphocytic inflammation. Moreover, lymphocytes and splenocytes harvested from sensitized animals pretreated in vivo with the NOP receptor agonist, had a proliferation index significantly lower compared to immune cells harvested from vehicle treated mice. No changes were measured in response to UFP-101 treatment. In this study we demonstrated for the first time the ability of a NOP receptor agonist to significantly reduce airway hyperresponsiveness induced by allergen exposure in an animal model of asthma. In particular, we show that NOP receptor agonist activity relies on the ability to interfere with the immune response that triggers the development of AHR.
Therefore, our study suggests NOP receptor agonists as possible novel therapeutic agents for controlling airway hyperesponsiveness associated with allergic disease.
The aim of this study was to investigate, in a conventional murine model of allergen-induced airway hyperresponsiveness (AHR), the role of N/OFQ signalling in the mechanism of allergen sensitization. BALB/c mice were treated intraperitoneally with the NOP receptor agonist UFP-112 or antagonist UFP-101 30 min before ovalbumin systemic sensitization. 21 days later, in vivo and in vitro bronchopulmonary function and lung cell counts were evaluated. In a separate set of experiments, on the 7th day after treatment, cell proliferation assay, cytokine levels and NOP receptor expression were evaluated in lymphocytes and splenocytes. Single administration of the UFP-112 at the time of sensitization significantly reduced AHR both in vivo and in vitro, with an improvement of eosinophylic and lymphocytic inflammation. Moreover, lymphocytes and splenocytes harvested from sensitized animals pretreated in vivo with the NOP receptor agonist, had a proliferation index significantly lower compared to immune cells harvested from vehicle treated mice. No changes were measured in response to UFP-101 treatment. In this study we demonstrated for the first time the ability of a NOP receptor agonist to significantly reduce airway hyperresponsiveness induced by allergen exposure in an animal model of asthma. In particular, we show that NOP receptor agonist activity relies on the ability to interfere with the immune response that triggers the development of AHR.
Therefore, our study suggests NOP receptor agonists as possible novel therapeutic agents for controlling airway hyperesponsiveness associated with allergic disease.
- D'Agostino B et al., (2010). Am J Respir Cell Mol Biol; 42:1-5