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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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Antigens, CD / metabolism
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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B7-1 Antigen / metabolism
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CD28 Antigens / metabolism
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CD4-Positive T-Lymphocytes / metabolism
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CHO Cells
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CTLA-4 Antigen
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Cricetinae
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Cricetulus
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme-Linked Immunosorbent Assay / methods
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Flow Cytometry / methods
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Gene Expression Regulation / drug effects
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Humans
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In Vitro Techniques
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Indomethacin / pharmacology
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Interleukin-6 / metabolism
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Lectins, C-Type
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Leukocytes, Mononuclear / drug effects
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Nociceptin
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Nociceptin Receptor
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Opioid Peptides / pharmacology*
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Prostaglandin D2 / pharmacology
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Receptors, Interleukin-2 / metabolism
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Receptors, Opioid / physiology
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / metabolism
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T-Lymphocytes / drug effects*
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T-Lymphocytes / physiology
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Thymidine / pharmacokinetics
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Transfection / methods
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Tritium / pharmacokinetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, CD
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Antigens, Differentiation
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Antigens, Differentiation, T-Lymphocyte
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B7-1 Antigen
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CD28 Antigens
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CD69 antigen
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CTLA-4 Antigen
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CTLA4 protein, human
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Cyclooxygenase Inhibitors
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Interleukin-6
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Lectins, C-Type
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Opioid Peptides
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Receptors, Interleukin-2
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Receptors, Opioid
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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TNFRSF10A protein, human
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Tumor Necrosis Factor-alpha
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Tritium
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Dinoprostone
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Prostaglandin D2
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Thymidine
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Indomethacin
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Nociceptin Receptor