Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription.
OBJECTIVE
Effects of cannabinoids are mediated by CB1 and CB2 receptors. In addition to neuronal effects, cannabinoids are potent modulators of immune functions. In this report, we investigated whether the transcription of these receptors is regulated after activation of T lymphocytes.


METHODS
CB1- and CB2-specific mRNA of primary human peripheral blood T cells and cells of the human T cell line Jurkat was measured by quantitative real-time RT-PCR in response to CD3/28. Using the decoy oligonucleotide approach, transcription factors involved in the regulation were determined. A promoter analysis was performed using transient transfection of chloramphenicol acetyl transferase reporter gene constructs in Jurkat cells.


RESULTS
Activation of human T cells caused an induction of CB1 mRNA expression in primary human T cells (8-fold) and Jurkat cells (29-fold). In contrast, CB2 transcription was not regulated. The CD3/28-mediated upregulation of CB1 involves the transcription factors AP-1, NF kappaB and NFAT. Furthermore, 2,490 bp of the CB1 promoter mediated inducibility in response to CD3/28.


CONCLUSIONS
The upregulation of CB1 in activated T cells, together with the constitutive expression of CB2, enables cellular responses to cannabinoids mediated by both receptor subtypes. It may thus contribute to the understanding of the various modulatory effects of cannabinoids on activated T cells.
Börner
Christine
C
Department of Pharmacology and Toxicology, University of Magdeburg, Magdeburg, Germany.
Höllt
Volker
V
Kraus
Jürgen
J
D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D018808:Transcription Factor AP-1