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

G. Spaziano, R. Sorrentino, M. Matteis, G. Malgieri, M. Sgambato, T. P. Russo, M. Terlizzi, F. Roviezzo, F. Rossi, A. Pinto, R. Fattorusso, B. D'Agostino

Research output: Contribution to journalArticle

Abstract

Background: Nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are involved in airway hyperresponsiveness (AHR) and inflammation. However, the role of nociceptin at modulating the inflammatory immune microenvironment in asthma is still unclear. Objective: To understand the role of N/OFQ in the regulation of a Th2-like environment, we used a conventional murine model of AHR. Methods: Balb/c and CD1 mice were sensitized to ovalbumin (OVA) and treated with saline solution or N/OFQ, at days 0 and 7. A group of Balb/c mice were killed at 7 and 14 days from the first sensitization for the inflammatory profile evaluation while a group of Balb/c and CD1 mice were aerosol-challenged from day 21 to 23 with OVA and killed 24 h later for functional evaluations. Results: In OVA-sensitized mice, N/OFQ significantly reduced IL-4+ CD4+ T cells in lymph nodes (LN) and IL-13 in the lungs, while it induced IFN-γ increase in the lung. The efflux of dendritic cells (DCs) to the mediastinic LN and into the lung of OVA-sensitized mice was reduced in N/OFQ-treated and sensitized mice. N/OFQ reduced the expression of CD80 on DCs, indicating its ability to modulate the activation of DCs. In a less prone Th2-like environment mice strain, such as CD1 mice, N/OFQ did not modify lung resistances as observed in BALB/c mice. Finally, spectroscopic data showed the N/OFQ was able to interact onto the membrane of DCs obtained from Balb/c rather than CD1 mice, indicating its ability to modulate AHR in a Th2-like environment with a direct activity on DCs. Conclusions and Clinical Relevance: Our data confirmed the capability of N/OFQ to modulate the immune microenvironment in the lung of Th2-biased, OVA-sensitized Balb/c mice, suggesting N/OFQ-NOP axis as a novel pharmacological tool to modulate the inflammatory immune microenvironment in asthma.

Original languageEnglish
JournalClinical and Experimental Allergy
DOIs
Publication statusAccepted/In press - 2016
Externally publishedYes

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • Dendritic cells
  • Th environment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Spaziano, G., Sorrentino, R., Matteis, M., Malgieri, G., Sgambato, M., Russo, T. P., Terlizzi, M., Roviezzo, F., Rossi, F., Pinto, A., Fattorusso, R., & D'Agostino, B. (Accepted/In press). Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness. Clinical and Experimental Allergy. https://doi.org/10.1111/cea.12808