QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 23, 2003, 23(16):6470-6474

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (46) Citing Articles via Google Scholar Google Scholar Articles by Molina-Holgado, F. Articles by Rothwell, N. J. Search for Related Content PubMed PubMed Citation Articles by Molina-Holgado, F. Articles by Rothwell, N. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Endogenous Interleukin-1 Receptor Antagonist Mediates Anti-Inflammatory and Neuroprotective Actions of Cannabinoids in Neurons and Glia

Francisco Molina-Holgado,¹ Emmanuel Pinteaux,¹ Jonathan D. Moore,¹ Eduardo Molina-Holgado,² Carmen Guaza,² Rosemary M. Gibson,¹ and Nancy J. Rothwell¹

¹School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom, and ²Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain

Interleukin-1 receptor antagonist (IL-1ra) is an important anti-inflammatory cytokine that blocks all known actions of IL-1 and markedly protects against experimentally induced ischemic, excitotoxic, and traumatic brain insults. Cannabinoids (CBs) also exert potent anti-inflammatory and neuroprotective effects, but the mechanisms of their actions are unknown. Here we tested the hypothesis that the actions of CBs are mediated by endogenous IL-1ra. We report for the first time that both CB₁ and CB₂ receptors modulate release of endogenous IL-1ra from primary cultured glial cells. Activation of CB₁ or CB₂ receptors increased lipopolysaccharide-induced IL-1ra release, and specific CB₁ or CB₂ antagonists blocked lipopolysaccharide-induced production of IL-1ra from glial cells. Comparison of neuronal cultures from wild-type mice and mice lacking IL-1ra (knock-out) indicates that endogenous IL-1ra is essential for the neuro-protective effects of CBs against excessive activation of glutamate receptors (excitotoxicity) in response to S-AMPA or NMDA. Similarly, analysis of mixed glial cultures from IL-1ra knock-out mice indicates that endogenous IL-1ra is required for the CB-induced inhibition of nitric oxide production in response to bacterial lipopolysaccharide. These data suggest a novel neuroprotective mechanism of action for CBs in response to inflammatory or excitotoxic insults that is mediated by both CB₁ and CB₂ receptor-dependent pathways.

Key words: cytokine; cannabinoid; neuroprotection; IL-1ra; excitotoxicity; nitric oxide

---

Received Mar. 25, 2003; revised May. 13, 2003; accepted Jun. 2, 2003.

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help