Canna~Fangled Abstracts

Cannabinoid CB2 receptor agonist AM1241 attenuates microglial activation by modulating the activated state in N9 microglia exposed to LPS plus IFNγ

By January 27, 2015No Comments
2015 Jan 27. pii: S0006-291X(15)00103-5. doi: 10.1016/j.bbrc.2015.01.073. [Epub ahead of print]

Ma L1, Jia J1, Liu X2, Bai F1, Wang Q3, Xiong L4.

Abstract

pm1Inhibition of microglial activation is effective in treating various neurological disorders. Activation of microglial cannabinoid CB2 receptor induces anti-inflammatory effects, and the mechanism, however, is still elusive. Microglia could be activated into the classic activated state (M1 state) or the alternative activated state (M2 state), the former is cytotoxic, and the latter is neurotrophic. In this study, we used lipopolysaccharide (LPS) plus interferon-γ (IFNγ) to activate N9 microglia and hypothesized the pretreatment with cannabinoid CB2 receptor agonist AM1241 attenuates microglial activation by shifting microglial M1 to M2 state. We found that pretreatment with 5 μM AM1241 at 1 h before microglia were exposed to LPS plus IFNγ decreased the expression of inducible nitric oxide synthase (iNOS) and the release of pro-inflammatory factors, increased the expression of arginase 1 (Arg-1) and the release of anti-inflammatory and neurotrophic factors in microglia. However, these effects induced by AM1241 pretreatment were significantly reversed in the presence of 10 μM cannabinoid CB2 receptor antagonist AM630 or 10 μM protein kinase C (PKC) inhibitor chelerythrine. These findings indicated that AM1241 pretreatment attenuates microglial activation by shifting M1 to M2 activated state via CB2 receptor, and the AM1241-induced anti-inflammatory effects may be mediated by PKC.
Copyright © 2015. Published by Elsevier Inc.

KEYWORDS:

Cannabinoid CB2 receptor; Inflammation; Microglia; Pretreatment; Protein kinase C

PMID:

 

25637536

 

[PubMed – as supplied by publisher] 
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