title: Nociceptin reduces the inflammatory immune microenvironment in a conventional murine model of airway hyperresponsiveness.
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
  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.
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: G
authors: G
authors: Spaziano
authors: Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, Italy.
authors: R
authors: R
authors: Sorrentino
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: M
authors: M
authors: Matteis
authors: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, Caserta, Italy.
authors: G
authors: G
authors: Malgieri
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: M
authors: M
authors: Sgambato
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: T P
authors: TP
authors: Russo
authors: Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, Italy.
authors: M
authors: M
authors: Terlizzi
authors: Department of Experimental Pharmacology, University Federico II of Naples, Naples, Italy.
authors: F
authors: F
authors: Roviezzo
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: F
authors: F
authors: Rossi
authors: Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, Italy.
authors: A
authors: A
authors: Pinto
authors: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, Caserta, Italy.
authors: R
authors: R
authors: Fattorusso
authors: Department of Experimental Medicine, Section of Pharmacology, Second University of Naples, Naples, Italy.
authors: B
authors: B
authors: D'Agostino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D060833:Cellular Microenvironment / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010641:Phenotype; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000097629:Nociceptin
chemical_list: D015415:Biomarkers; D018847:Opioid Peptides; D010047:Ovalbumin; D000097629:Nociceptin
keywords: Th2 environment; airway hyperresponsiveness; asthma; dendritic cells