title: Kappa-opioid regulation of thymocyte IL-7 receptor and C-C chemokine receptor 2 expression.
abstract: Endogenous and exogenous kappa-opioid agonists have been widely reported to modulate the immune response. We have published results that show that the superantigen-induced proliferative response of thymocytes is inhibited by the selective kappa-opioid agonist trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl] benzeneaceamide methanesulfonate (U50,488H). Previous work has established that the kappa-opioid receptor is widely expressed within the thymus; however, little is known about the role of the kappa-opioid receptor in the function of thymocytes. In the present report, we have examined the impact of U50,488H administration on the expression of cytokines in superantigen-stimulated thymocytes by RNase protection analysis. We have measured detectable levels of the cytokines IL-2, IL-4, IL-5, IL-13, and IFN-gamma, and the chemokines lymphotactin and RANTES, in stimulated thymocyte cultures; however, addition of U50,488H did not alter the expression of these cytokines. Examination of cytokine receptor expression by these thymocytes revealed a significant inhibition in the expression of the transcript for the IL-7 receptor alpha-chain (IL-7Ralpha), and these results were confirmed by flow cytometry. Surprisingly, the expression of several other cytokine receptor chains including the common gamma-chain, IL-2Rbeta, or the IL-2Ralpha, IL-4Ralpha, and IL-15Ralpha chains, was not altered. In contrast to these results, a significant elevation in the expression of the chemokine receptor CCR2 was observed in U50,488H-treated cultures. These results suggest that the kappa-opioid receptor may function to promote cellular migration at the expense of the sensitivity to the growth-promoting/maturation activity of IL-7.
authors.affiliation: Department of Microbiology, Fels Institute for Cancer Research and Molecular Biology, Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: T J
authors.initials: TJ
authors.lastname: Rogers
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: C515335:Ccr2 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D020395:Receptors, Interleukin-7; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer