TY - JOUR
T1 - Downregulation of class II transactivator (CIITA) expression by synthetic cannabinoid CP55,940
AU - Gongora, Celine
AU - Hose, Stacey
AU - O'Brien, Terrence P.
AU - Sinha, Debasish
N1 - Funding Information:
We thank Dr. S. Zigler for his support during the course of this study, Dr. M. Herkenham for providing CP55,940, Dr. T. Bonner and Professor Avi Nath for critical review of the manuscript and helpful discussions. Celine Gongora was supported by grants from the French Association pour la Recherche sur le Cancer.
PY - 2004/1/30
Y1 - 2004/1/30
N2 - Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-γ induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-γ. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-γ induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.
AB - Cannabinoid receptors are known to be expressed in microglia; however, their involvement in specific aspects of microglial immune function has not been demonstrated. Many effects of cannabinoids are mediated by two G-protein coupled receptors, designated CB1 and CB2. We have shown that the CB1 receptor is expressed in microglia that also express MHC class II antigen (J. Neuroimmunol. 82 (1998) 13-21). In our present study, we have analyzed the effect of cannabinoid agonist CP55,940 on MHC class II expression on the surface of IFN-γ induced microglial cells by flow cytometry. CP55,940 blocked the class II MHC expression induced by IFN-γ. It has been shown that the regulation of class II MHC genes occurs primarily at the transcriptional level, and a non-DNA binding protein, class II transactivator (CIITA), has been shown to be the master activator for class II transcription. We find that mRNA levels of CIITA are increased in IFN-γ induced EOC 20 microglial cells and that this increase is almost entirely eliminated by the cannabinoid agonist CP55,940. These data suggests that cannabinoids affect MHC class II expression through actions on CIITA at the transcriptional level.
KW - CB1 cannabinoid receptor
KW - CIITA class II MHC
KW - CP55,940
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U2 - 10.1016/j.imlet.2003.09.006
DO - 10.1016/j.imlet.2003.09.006
M3 - Article
C2 - 14757364
AN - SCOPUS:0742306865
SN - 0165-2478
VL - 91
SP - 11
EP - 16
JO - Immunology Letters
JF - Immunology Letters
IS - 1
ER -