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Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells.
Mol Pharmacol. 2006 Apr; 69(4):1486-91.MP

Abstract

Opioids and cannabinoids are both associated with analgetic, psychotropic, and immunomodulatory effects. It has been suggested that both systems interact on multiple levels. We hypothesized that cannabinoids induce opioid receptors and investigated cannabinoid-dependent expression of the mu-opioid receptor subtype in a human T cell model. We report that activation of the peripheral cannabinoid receptor type 2 leads to a de novo induction of mu-opioid receptor transcription in Jurkat E6.1 cells. We show that interleukin-4 is transcriptionally induced in response to cannabinoids and that an interleukin-4 receptor antagonist blocks cannabinoid-dependent induction of mu-opioid receptors, indicating that induced expression of interleukin-4 is required in this process. Induction of interleukin-4 is blocked by decoy oligonucleotides directed against STAT5, indicating the requirement of this transcription factor. In addition, we show cannabinoid-dependent phosphorylation of STAT5. Further experiments demonstrate that interleukin-4 then induces phosphorylation of STAT6, which directly transactivates the mu-opioid receptor gene. In addition, STAT6 induces expression of the transcription factor GATA3, which also contributes to mu-opioid receptor gene transcription. The responsive promoter region of the human mu-opioid receptor gene with the binding sites for both factors was mapped to nt -1001 to -950. To demonstrate functional mu-opioid receptor proteins, morphine-mediated phosphorylation of mitogen-activated protein kinase was investigated. We show that phosphorylation of mitogen-activated protein kinase occurs only in cannabinoid-prestimulated Jurkat E6.1 cells and that it is blocked by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. In summary, these findings provide a first example for cannabinoid-opioid-interactions in cells of the immune system.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, University of Magdeburg, 44 Leipziger Strasse, 39120 Magdeburg, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16434616

Citation

Börner, Christine, et al. "Cannabinoid Receptor Type 2 Agonists Induce Transcription of the Mu-opioid Receptor Gene in Jurkat T Cells." Molecular Pharmacology, vol. 69, no. 4, 2006, pp. 1486-91.
Börner C, Höllt V, Kraus J. Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Mol Pharmacol. 2006;69(4):1486-91.
Börner, C., Höllt, V., & Kraus, J. (2006). Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Molecular Pharmacology, 69(4), 1486-91.
Börner C, Höllt V, Kraus J. Cannabinoid Receptor Type 2 Agonists Induce Transcription of the Mu-opioid Receptor Gene in Jurkat T Cells. Mol Pharmacol. 2006;69(4):1486-91. PubMed PMID: 16434616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. AU - Börner,Christine, AU - Höllt,Volker, AU - Kraus,Jürgen, Y1 - 2006/01/24/ PY - 2006/1/26/pubmed PY - 2006/6/20/medline PY - 2006/1/26/entrez SP - 1486 EP - 91 JF - Molecular pharmacology JO - Mol Pharmacol VL - 69 IS - 4 N2 - Opioids and cannabinoids are both associated with analgetic, psychotropic, and immunomodulatory effects. It has been suggested that both systems interact on multiple levels. We hypothesized that cannabinoids induce opioid receptors and investigated cannabinoid-dependent expression of the mu-opioid receptor subtype in a human T cell model. We report that activation of the peripheral cannabinoid receptor type 2 leads to a de novo induction of mu-opioid receptor transcription in Jurkat E6.1 cells. We show that interleukin-4 is transcriptionally induced in response to cannabinoids and that an interleukin-4 receptor antagonist blocks cannabinoid-dependent induction of mu-opioid receptors, indicating that induced expression of interleukin-4 is required in this process. Induction of interleukin-4 is blocked by decoy oligonucleotides directed against STAT5, indicating the requirement of this transcription factor. In addition, we show cannabinoid-dependent phosphorylation of STAT5. Further experiments demonstrate that interleukin-4 then induces phosphorylation of STAT6, which directly transactivates the mu-opioid receptor gene. In addition, STAT6 induces expression of the transcription factor GATA3, which also contributes to mu-opioid receptor gene transcription. The responsive promoter region of the human mu-opioid receptor gene with the binding sites for both factors was mapped to nt -1001 to -950. To demonstrate functional mu-opioid receptor proteins, morphine-mediated phosphorylation of mitogen-activated protein kinase was investigated. We show that phosphorylation of mitogen-activated protein kinase occurs only in cannabinoid-prestimulated Jurkat E6.1 cells and that it is blocked by the mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. In summary, these findings provide a first example for cannabinoid-opioid-interactions in cells of the immune system. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/16434616/Cannabinoid_receptor_type_2_agonists_induce_transcription_of_the_mu_opioid_receptor_gene_in_Jurkat_T_cells_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16434616 DB - PRIME DP - Unbound Medicine ER -