DELTA-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/

Recent molecular evidence points to transient and/or stage-specific ex pression of delta- and kappa-opioid receptors by thymic and peripheral T lymphocytes. Since medical treatments or stress commonly increase o pioid levels, it is important to understand the mechanisms by which op ioids affect T lymphocyte functions. We therefore created and studied a T cell line expressing the cloned delta-opioid receptor (DOR1). DOR1 ligation by a specific DOR1 agonist, deltorphin, augmented IL-2 secre tion 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 signalin g increased [Ca2+](i), deltorphin enhanced transcriptional activity of the NF-AT/AP-1-binding site via a mechanism independent of calcineuri n and distinct from the effects of elevated [Ca2+](i). Deltorphin also increased accumulation of AP-1 transcription factor complexes, sugges ting that DOR1 augments IL-2 secretion by increasing the AP-1 componen t of the NF-AT/AP-1 transcription factor. These results advance the mo lecular understanding of opioid effects on lymphocytes, and in additio n, demonstrate regulation of IL-2 synthesis and secretion by the novel mechanism of receptor-mediated AP-1 induction.