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Activation of type-2 cannabinoid receptor inhibits neuroprotective and antiinflammatory actions of glucocorticoid receptor α: when one is better than two.
MedLine Citation:
PMID:  23296125     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Endocannabinoids (eCBs) and glucocorticoids (GCs) are two distinct classes of signaling lipids that exert both neuroprotective and immunosuppressive effects; however, the possibility of an actual interaction of their receptors [i.e., type-2 cannabinoid (CB(2)) and glucocorticoid receptor α (GRα), respectively] remains unexplored. Here, we demonstrate that the concomitant activation of CB(2) and GRα abolishes the neuroprotective effects induced by each receptor on central neurons and on glial cells in animal models of remote cell death. We also show that the ability of eCBs and GCs, used individually, to inhibit tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production from activated human T lymphocytes is lost when CB(2) and GRα are activated simultaneously. In addition, signal transduction pathways triggered by concomitant activation of both receptors led to increased levels of GRβ, heat-shock proteins-70 and -90, and p-JNK, as well as to reduced levels of p-STAT6. These effects were reversed only by selectively antagonizing CB(2), but not GRα. Overall, our study demonstrates for the first time the existence of a CB(2)-driven negative cross-talk between eCB and GC signaling in both rats and humans, thus paving the way to the possible therapeutic exploitation of CB(2) as a new target for chronic inflammatory and neurodegenerative diseases.
Authors:
Elisa Bisicchia; Valerio Chiurchiù; Maria Teresa Viscomi; Laura Latini; Filomena Fezza; Luca Battistini; Mauro Maccarrone; Marco Molinari
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-8
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  -     ISSN:  1420-9071     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100, Teramo, Italy.
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