Abstract
Background: Nociceptin/Orphanin FQ (N/OFQ) is an endogenous heptadecapeptide that selectively binds the NOP receptor involved in the airways hyperresponsiveness (AHR) and in the regulation of the inflammatory response.
Aim and objectives: Understand the role of the N/OFQ-NOP system in the regulation of a Th2-like environment in a murine model of AHR.
Methods: Balb/c and CD1 mice were sensitized with i.p. ovalbumin (OVA) and treated with saline solution or N/OFQ at day 0 and 7. At 1, 3, 7 and 14 days from the first allergen exposure tissues were collected for cellular evaluation. At 21th day functional and cellular evaluation were performed.
Results: In OVA-sensitized Balb/c mice, N/OFQ significantly reduces Dendritic cells (DCs) influx and in LPS-treated primary bone marrow-derived DCs, obtained from OVA-sensitized Balb/c mice, significantly reduce the levels of MHC I/II. In OVA- sensitized CD1 mice which are less prone compared to BALB/c to the Th2-like environment, N/OFQ didn't modify the lung resistances as observed in BALB/c mice. Moreover, spectroscopic data, further support the effect of N/OFQ on innate immune cells, showing the N/OFQ ability to interact with DCs obtained from Balb/c rather than CD1 mice. Finally, N/OFQ significantly reduces pro-inflammatory cytokines and pulmonary macrophages in OVA-sensitized Balb/c mice, suggesting its potential implication in the regulation of the inflammatory response also.
Conclusions: These results confirming our previous data further demonstrate that NOP receptor expression regulation and its activation by N/OFQ, may significantly modulate the inflammatory immune microenvironment in a conventional murine model of asthma.
- Copyright ©ERS 2015
