Journal article
Cannabinoids Delta(9)-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-kappa B and Interferon-beta/STAT Proinflammatory Pathways in BV-2 Microglial Cells
Journal of Biological Chemistry, Vol.285(3), pp.1616-1626
Jan/2010
Abstract
Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1 beta, interleukin-6, and interferon (IFN)beta, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-kappa B pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFN beta-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-kappa B and IFN beta-dependent pathways.
Details
- Title
- Cannabinoids Delta(9)-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-kappa B and Interferon-beta/STAT Proinflammatory Pathways in BV-2 Microglial Cells
- Creators
- Ewa Kozela (null)Maciej Pietr (null)Ana Juknat (null)Neta Rimmerman (null) - The Weizmann Institute of ScienceRivka Levy (null) - The Weizmann Institute of ScienceZvi Vogel (null) - The Weizmann Institute of Science
- Resource Type
- Journal article
- Publication Details
- Journal of Biological Chemistry, Vol.285(3), pp.1616-1626; Jan/2010
- Number of pages
- 11
- Language
- English
- DOI
- https://doi.org/10.1074/jbc.M109.069294
- Grant note
- Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases; Adelsons' Program for Nerve Regeneration and Repair; Nella and Leon Benoziyo Center for Neurosciences; Israeli Ministry of HealthThis work was supported in part by the Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, by the Adelsons' Program for Nerve Regeneration and Repair, by the Nella and Leon Benoziyo Center for Neurosciences, and by the Israeli Ministry of Health (to Z. V.)._ALMAME_DELIMITER_
- Scientific Unit
- The Weizmann Institute of Science
- Record Identifier
- 993263474203596
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