title: Nociceptin/orphanin FQ-NOP receptor system in inflammatory and immune-mediated diseases.
abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the G-protein-coupled receptor NOP. Cells from the immune system express the precursor preproN/OFQ and the NOP receptor, as well as secrete N/OFQ. The activation of the N/OFQ-NOP pathway can regulate inflammatory and immune responses. Several immune activities, including leukocyte migration, cytokine and chemokine production, and lymphocytes proliferation are influenced by NOP activation. It was demonstrated that cytokines and other stimuli such as Toll-like receptor agonist (e.g., lipopolysaccharide) induce N/OFQ production by cells from innate and adaptive immune response. In this context, N/OFQ could modulate the outcome of inflammatory diseases, such as sepsis and immune-mediated pathologies by mechanisms not clearly elucidated. In fact, clinical studies revealed increased levels of N/OFQ under sepsis, arthritis, and Parkinson's disease. Preclinical and clinical studies pointed to the blockade of NOP receptor signaling as successful strategy for the treatment of inflammatory diseases. This review is focused on experimental and clinical data that suggest the participation of N/OFQ-NOP receptor activation in the modulation of the immune response, highlighting the immunomodulatory potential of NOP antagonists in the inflammatory and immunological disturbances.
authors: Department of Biophysic and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors: Elaine C
authors: EC
authors: Gavioli
authors: Department of Biophysic and Pharmacology, Federal University of Rio Grande do Norte, Natal, Brazil.
authors: Iris Ucella
authors: IU
authors: de Medeiros
authors: Laboratory of Clinical Microbiology and Immunology, Faculty of Pharmacy, Federal University of Pará, Belém, Brazil.
authors: Marta C
authors: MC
authors: Monteiro
authors: Department of Medical Sciences, Section of Pharmacology and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors: Girolamo
authors: G
authors: Calo
authors: Laboratory of Immunology, Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Rua Sarmento Leite, Porto Alegre, Brazil. Electronic address: pedror@ufcspa.edu.br.
authors: Pedro R T
authors: PR
authors: Romão
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D018448:Models, Immunological; D018847:Opioid Peptides / Q000378:metabolism*; D018384:Oxidative Stress; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
keywords: Arthritis; Colitis; Cytokines; Immunoregulation; Inflammatory and autoimmune diseases; NOP receptor; Nociceptin/orphanin FQ; Parkinson's disease; Sepsis