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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. [ABSTRACT FROM AUTHOR]

Conformational constrained β-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the β-hairpin peptide. The entity of the stability of the β-hairpin peptide depends on the length of the bridge. [ABSTRACT FROM AUTHOR]