Nociceptin/orphanin FQ modulates human T cell function in vitro

• Published in: Journal of neuroimmunology 2004-04, Vol.149 (1), p.110-120
• Main Authors: Waits, Paula S., Purcell, Wendy M., Fulford, Allison J., McLeod, Julie D.
• Format: Article
• Language: English
• Subjects: Activation markers; Adult; Animals; Antigens, CD - metabolism; Antigens, Differentiation - genetics; Antigens, Differentiation - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; B7-1 Antigen - metabolism; CD28 Antigens - metabolism; CD4-Positive T-Lymphocytes - metabolism; CHO Cells; Cricetinae; Cricetulus; CTLA-4 Antigen; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Enzyme-Linked Immunosorbent Assay - methods; Flow Cytometry - methods; Gene Expression Regulation - drug effects; Humans; In Vitro Techniques; Indomethacin - pharmacology; Interleukin-6 - metabolism; Lectins, C-Type; Leukocytes, Mononuclear - drug effects; Neuropeptides; Nociceptin; Nociceptin Receptor; Opioid Peptides - pharmacology; Prostaglandin; Prostaglandin D2 - pharmacology; Receptors, Interleukin-2 - metabolism; Receptors, Opioid - physiology; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor - metabolism; T cell; T-Lymphocytes - drug effects; T-Lymphocytes - physiology; Thymidine - pharmacokinetics; Transfection - methods; Tritium - pharmacokinetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2003.12.018

Although nociceptin/orphanin FQ (N/OFQ) and its receptor (ORL-1) are widely distributed throughout the immune system, its role has yet to be elucidated. This study shows that N/OFQ (10 −14–10 −12 M) modulates T cell activation by up-regulating activation marker expression, e.g. CD28, leading to enhanced proliferation and modulation of TNFα secretion. However, on re-stimulated T cells N/OFQ causes inhibition of proliferation, which could be linked with N/OFQ up-regulating CTLA-4 expression. We have also shown that some of these effects are partly prostaglandin-dependent and that N/OFQ induces prostaglandin synthesis. This report suggests that N/OFQ could exert a key modulatory role in human T cell functions.