ABSTRACT
Previous research has demonstrated that numerous populations of immune cell, including lymphocytes, synthesize nociceptin (N/OFQ) precursor mRNA although little is known regarding the immunological role of N/OFQ. In the present study we have demonstrated significant effects of mitogens, pro-inflammatory cytokines, cyclic AMP analogues, glucocorticoids and CRF on N/OFQ secretion by rat splenocytes in vitro. N/OFQ (10(-14) to 10(-10)M) was also shown to inhibit proliferation of Con A-activated splenocytes and production of IL-2 in vitro. In summary we have shown how a variety of stimuli relevant to inflammation can regulate endogenous N/OFQ secretion by splenocytes in vitro. We also suggest that N/OFQ may promote anti-inflammatory actions via suppression of IL-2 in vivo.
Subject(s)
Interleukin-2/metabolism , Lymphocytes/metabolism , Opioid Peptides/metabolism , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Analysis of Variance , Animals , Cell Proliferation/drug effects , Cells, Cultured , Dexamethasone/pharmacology , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Glucocorticoids/pharmacology , Interleukin-1beta/pharmacology , Lipopolysaccharides/pharmacology , Lymphocytes/cytology , Lymphocytes/drug effects , Male , Opioid Peptides/pharmacology , Rats , Rats, Wistar , Receptors, Glucocorticoid/antagonists & inhibitors , Spleen/cytology , Spleen/drug effects , Spleen/metabolism , Tumor Necrosis Factor-alpha/pharmacology , NociceptinABSTRACT
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.