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Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation

Authors
  • Ehrhart, Jared1
  • Obregon, Demian1
  • Mori, Takashi1, 2
  • Hou, Huayan1
  • Sun, Nan1
  • Bai, Yun1, 3
  • Klein, Thomas4
  • Fernandez, Francisco1
  • Tan, Jun1, 4, 5, 6
  • Shytle, R Douglas1, 5, 6
  • 1 University of South Florida College of Medicine, Neuroimmunlogy Laboratory, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, Tampa, FL, 33613, USA , Tampa
  • 2 Saitama Medical School, Institute of Medical Science, Saitama, 350-8550, Japan , Saitama
  • 3 the Third Medical University, Department of Molecular Genetics, Chongqing, China , Chongqing
  • 4 University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa, FL, 33613, USA , Tampa
  • 5 University of South Florida College of Medicine, Center for Excellence in Aging and Brain Repair, Department of Neurosurgery, Tampa, FL, 33613, USA , Tampa
  • 6 University of South Florida College of Medicine, Department of Pharmacology and Therapeutics, Tampa, FL, 33613, USA , Tampa
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 12, 2005
Volume
2
Issue
1
Identifiers
DOI: 10.1186/1742-2094-2-29
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundActivated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB2).MethodsIn this study, we investigated the effects of a cannabinoid agonist on CD40 expression and function by cultured microglial cells activated by IFN-γ using RT-PCR, Western immunoblotting, flow cytometry, and anti-CB2 small interfering RNA (siRNA) analyses. Furthermore, we examined if the stimulation of CB2 could modulate the capacity of microglial cells to phagocytise Aβ1–42 peptide using a phagocytosis assay.ResultsWe found that the selective stimulation of cannabinoid receptor CB2 by JWH-015 suppressed IFN-γ-induced CD40 expression. In addition, this CB2 agonist markedly inhibited IFN-γ-induced phosphorylation of JAK/STAT1. Further, this stimulation was also able to suppress microglial TNF-α and nitric oxide production induced either by IFN-γ or Aβ peptide challenge in the presence of CD40 ligation. Finally, we showed that CB2 activation by JWH-015 markedly attenuated CD40-mediated inhibition of microglial phagocytosis of Aβ1–42 peptide. Taken together, these results provide mechanistic insight into beneficial effects provided by cannabinoid receptor CB2 modulation in neurodegenerative diseases, particularly AD.

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