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J Neuroimmunol ; 149(1-2): 110-20, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15020071

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.


Subject(s)
Opioid Peptides/pharmacology , T-Lymphocytes/drug effects , 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 , CTLA-4 Antigen , Cricetinae , Cricetulus , 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 , Prostaglandin D2/pharmacology , Receptors, Interleukin-2/metabolism , Receptors, Opioid/physiology , Receptors, TNF-Related Apoptosis-Inducing Ligand , Receptors, Tumor Necrosis Factor/metabolism , T-Lymphocytes/physiology , Thymidine/pharmacokinetics , Transfection/methods , Tritium/pharmacokinetics , Tumor Necrosis Factor-alpha/metabolism , Nociceptin Receptor , Nociceptin
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