Tags

Type your tag names separated by a space and hit enter

Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids.

Abstract

Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and CB2. In this report, we investigated whether CBs regulate gene expression of their cognate receptors in T cells and studied underlying mechanisms in CD4+ Jurkat T cells. Transcription of the CB1 gene was strongly induced in response to Delta9-tetrahydrocannabinol (THC), whereas the CB2 gene was not regulated. The induction of CB1 gene expression is mediated by CB2 receptors only, as demonstrated by using the CB1 and CB2 agonists R(+)-methanandamide and JWH 015, respectively, and combinations of THC plus CB1- and CB2-specific antagonists. After activation of CB2 receptors, the transcription factor STAT5 is phosphorylated. STAT5 then transactivates IL-4. Induction of IL-4 mRNA as well as IL-4 protein release from the cells are necessary for the following induction of the CB1 gene. This was demonstrated by using decoy oligonucleotides against STAT5, which blocked IL-4 and CB1 mRNA induction, and by using the IL-4 receptor antagonist IL-4 [R121D,Y124D], which blocked the up-regulation of CB1 gene transcription. Transactivation of the CB1 gene in response to IL-4 is then mediated by the transcription factor STAT6, as shown by using decoy oligonucleotides against STAT6. An increase in CB1-mediated phosphorylation of MAPK in cells prestimulated with CB2-specific agonists suggests up-regulation of functional CB1 receptor proteins. In summary, up-regulation of CB1 in T lymphocytes in response to CBs themselves may facilitate or enhance the various immunomodulatory effects related to CBs.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pharmacology and Toxicology, University of Magdeburg, Leipzigerstr. 44, 39120 Magdeburg, Germany.

    , ,

    Source

    Journal of leukocyte biology 81:1 2007 Jan pg 336-43

    MeSH

    Cannabinoids
    Cell Line, Tumor
    Dronabinol
    Drug Synergism
    GATA3 Transcription Factor
    Humans
    Interleukin-13
    Interleukin-4
    Jurkat Cells
    RNA, Messenger
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    T-Lymphocytes
    Time Factors
    Transcription Factors
    Transcription, Genetic

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17041005

    Citation

    Börner, Christine, et al. "Transcriptional Regulation of the Cannabinoid Receptor Type 1 Gene in T Cells By Cannabinoids." Journal of Leukocyte Biology, vol. 81, no. 1, 2007, pp. 336-43.
    Börner C, Höllt V, Sebald W, et al. Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. J Leukoc Biol. 2007;81(1):336-43.
    Börner, C., Höllt, V., Sebald, W., & Kraus, J. (2007). Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. Journal of Leukocyte Biology, 81(1), pp. 336-43.
    Börner C, et al. Transcriptional Regulation of the Cannabinoid Receptor Type 1 Gene in T Cells By Cannabinoids. J Leukoc Biol. 2007;81(1):336-43. PubMed PMID: 17041005.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Transcriptional regulation of the cannabinoid receptor type 1 gene in T cells by cannabinoids. AU - Börner,Christine, AU - Höllt,Volker, AU - Sebald,Walter, AU - Kraus,Jürgen, Y1 - 2006/10/13/ PY - 2006/10/17/pubmed PY - 2007/3/6/medline PY - 2006/10/17/entrez SP - 336 EP - 43 JF - Journal of leukocyte biology JO - J. Leukoc. Biol. VL - 81 IS - 1 N2 - Effects of cannabinoids (CBs) are mediated by two types of receptors, CB1 and CB2. In this report, we investigated whether CBs regulate gene expression of their cognate receptors in T cells and studied underlying mechanisms in CD4+ Jurkat T cells. Transcription of the CB1 gene was strongly induced in response to Delta9-tetrahydrocannabinol (THC), whereas the CB2 gene was not regulated. The induction of CB1 gene expression is mediated by CB2 receptors only, as demonstrated by using the CB1 and CB2 agonists R(+)-methanandamide and JWH 015, respectively, and combinations of THC plus CB1- and CB2-specific antagonists. After activation of CB2 receptors, the transcription factor STAT5 is phosphorylated. STAT5 then transactivates IL-4. Induction of IL-4 mRNA as well as IL-4 protein release from the cells are necessary for the following induction of the CB1 gene. This was demonstrated by using decoy oligonucleotides against STAT5, which blocked IL-4 and CB1 mRNA induction, and by using the IL-4 receptor antagonist IL-4 [R121D,Y124D], which blocked the up-regulation of CB1 gene transcription. Transactivation of the CB1 gene in response to IL-4 is then mediated by the transcription factor STAT6, as shown by using decoy oligonucleotides against STAT6. An increase in CB1-mediated phosphorylation of MAPK in cells prestimulated with CB2-specific agonists suggests up-regulation of functional CB1 receptor proteins. In summary, up-regulation of CB1 in T lymphocytes in response to CBs themselves may facilitate or enhance the various immunomodulatory effects related to CBs. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/17041005/Transcriptional_regulation_of_the_cannabinoid_receptor_type_1_gene_in_T_cells_by_cannabinoids_ L2 - https://doi.org/10.1189/jlb.0306224 DB - PRIME DP - Unbound Medicine ER -