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J. Biol. Chem., Vol. 277, Issue 15, 12854-12860, April 12, 2002
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-Opioid Receptor Gene
-OPIOID RECEPTOR GENE IN ACTIVATED T CELLS*
and
From the Department of Pharmacology, University of Minnesota
Medical School, Minneapolis, Minnesota 55455
-Opioid receptors (DOR) present on T cells
have been shown to mediate the immunomodulatory effects of endogenous
and synthetic DOR agonists on T cells. Considerable evidence indicates
that there is stimulated transcription of DOR gene in activated
T cells, which is correlated with augmented expression of DOR and
enhanced capacity of DOR agonists to affect the T-cell's functions.
However, the molecular mechanism underlying the stimulated
transcription of the DOR gene in activated T cells is still
unclear. In the present study, we analyzed a 1.3-kb DNA fragment
immediately upstream of the translation start site (
1300 to +1 bp,
with the translation start site designated as +1) of the mouse DOR gene
in EL-4 cells, a mouse lymphoma T cell line that exhibits enhanced
expression of DOR transcripts when activated by phytohemagglutinin.
Through both in vivo and in vitro experiments,
we have demonstrated that increased binding activity of Ikaros at the
Ikaros-binding site (378 to 374) in the DOR promoter is required
for the stimulated transcription of DOR gene in
phytohemagglutinin-activated T cells.
To whom correspondence should be addressed: Dept. of Pharmacology,
University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church
St. S.E., Minneapolis, MN 55455. Tel.: 612-626-6539; Fax: 612-625-8408;
E-mail: sunx0078@tc.umn.edu.
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