κ-Opioid Regulation of Thymocyte IL-7 Receptor and C-C Chemokine Receptor 2 Expression

Abstract

Endogenous and exogenous κ-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 κ-opioid agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488H). Previous work has established that the κ-opioid receptor is widely expressed within the thymus; however, little is known about the role of the κ-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-γ, 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 α-chain (IL-7Rα), and these results were confirmed by flow cytometry. Surprisingly, the expression of several other cytokine receptor chains including the common γ-chain, IL-2Rβ, or the IL-2Rα, IL-4Rα, and IL-15Rα 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 κ-opioid receptor may function to promote cellular migration at the expense of the sensitivity to the growth-promoting/maturation activity of IL-7.