δ-Opioid Receptors Expressed by Jurkat T Cells Enhance IL-2 Secretion by Increasing AP-1 Complexes and Activity of the NF-AT/AP-1-Binding Promoter Element

Karen E. Hedin, Michael P. Bell, Kimberly R. Kalli, Catherine J. Huntoon, Burt Sharp, David J. McKean

Research output: Contribution to journalArticle

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Abstract

Recent molecular evidence points to transient and/or stage-specific expression of δ- and κ-opioid receptors by thymic and peripheral T lymphocytes. Since medical treatments or stress commonly increase opioid levels, it is important to understand the mechanisms by which opioids affect T lymphocyte functions. We therefore created and studied a T cell line expressing the cloned δ-opioid receptor (DOR1). DOR1 ligation by a specific DOR1 agonist, deltorphin, augmented IL-2 secretion by synergizing with signals from TCR-CD3 and CD28. Reporter gene constructs were used to map this effect of deltorphin to the AP-1- and NF-AT/AP-1-binding sites of the IL-2 promoter. Although DOR1 signaling increased [Ca2+]i, deltorphin enhanced transcriptional activity of the NF-AT/AP-1-binding site via a mechanism independent of calcineurin and distinct from the effects of elevated [Ca2+]i. Deltorphin also increased accumulation of AP-1 transcription factor complexes, suggesting that DOR1 augments IL-2 secretion by increasing the AP-1 component of the NF-AT/AP-1 transcription factor. These results advance the molecular understanding of opioid effects on lymphocytes, and in addition, demonstrate regulation of IL-2 synthesis and secretion by the novel mechanism of receptor-mediated AP-1 induction.

Original languageEnglish (US)
Pages (from-to)5431-5440
Number of pages10
JournalJournal of Immunology
Volume159
Issue number11
StatePublished - Dec 1 1997

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Jurkat Cells
Transcription Factor AP-1
Opioid Receptors
Interleukin-2
T-Lymphocytes
Opioid Analgesics
Binding Sites
Calcineurin
Reporter Genes
Ligation
Lymphocytes
Cell Line
deltorphin

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

δ-Opioid Receptors Expressed by Jurkat T Cells Enhance IL-2 Secretion by Increasing AP-1 Complexes and Activity of the NF-AT/AP-1-Binding Promoter Element. / Hedin, Karen E.; Bell, Michael P.; Kalli, Kimberly R.; Huntoon, Catherine J.; Sharp, Burt; McKean, David J.

In: Journal of Immunology, Vol. 159, No. 11, 01.12.1997, p. 5431-5440.

Research output: Contribution to journalArticle

Hedin, Karen E. ; Bell, Michael P. ; Kalli, Kimberly R. ; Huntoon, Catherine J. ; Sharp, Burt ; McKean, David J. / δ-Opioid Receptors Expressed by Jurkat T Cells Enhance IL-2 Secretion by Increasing AP-1 Complexes and Activity of the NF-AT/AP-1-Binding Promoter Element. In: Journal of Immunology. 1997 ; Vol. 159, No. 11. pp. 5431-5440.
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