Title
Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness
Author
Giuseppe Spaziano, Rosalinda Sorrentino, Maria Matteis, Gaetano Malgieri, Manuela Sgambato, Teresa Palmira Russo, Michela Terlizzi, Fiorentina Roviezzo, Francesco Rossi, Aldo Pinto, Roberto Fattorusso, Bruno D'Agostino
Year
2016
Journal
Clinical & Experimental Allergy
Abstract
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. To understand the role of N/OFQ in the regulation of a Th2-like environment we used a conventional murine model of AHR. 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 sacrificed 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 sacrificed 24 hours later for functional evaluations. 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 were 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 didn't 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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry