title: Nociceptin/orphanin FQ modulates human T cell function in vitro.
abstract: 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 TNFalpha 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.
authors.affiliation: Faculty of Applied Sciences, Centre for Research in Biomedicine, University of the West of England, Coldharbour Lane, Frenchay, Bristol, BS16 1QY, UK.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Waits
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Purcell
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Fulford
authors.forename: Julie D
authors.initials: JD
authors.lastname: McLeod
mesh_terms: D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016466:CHO Cells; D060908:CTLA-4 Antigen; D006224:Cricetinae; D003412:Cricetulus; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011957:Receptors, Opioid / Q000502:physiology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013936:Thymidine / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods; D014316:Tritium / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D007213:Indomethacin; D015850:Interleukin-6; D037181:Lectins, C-Type; D018847:Opioid Peptides; D015230:Prostaglandin D2; D015375:Receptors, Interleukin-2; D011957:Receptors, Opioid; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D013936:Thymidine; D014316:Tritium; D014409:Tumor Necrosis Factor-alpha; D000094942:Nociceptin Receptor; D000097629:Nociceptin; D000099192:CD69 Antigens; C556706:CTLA4 protein, human; C105190:TNFRSF10A protein, human