title: Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling.
abstract: Inhibition 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.
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Lei
authors: L
authors: Ma
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Ji
authors: J
authors: Jia
authors: Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Xiangyu
authors: X
authors: Liu
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors: Fuhai
authors: F
authors: Bai
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: wangqiang@fmmu.edu.cn.
authors: Qiang
authors: Q
authors: Wang
authors: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address: mzkxlz@126.com.
authors: Lize
authors: L
authors: Xiong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001119:Arginase / Q000378:metabolism; D053119:Benzophenanthridines / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D002460:Cell Line; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C439263:AM 1241; D000893:Anti-Inflammatory Agents; D053119:Benzophenanthridines; D019208:Brain-Derived Neurotrophic Factor; D002186:Cannabinoids; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007211:Indoles; D008070:Lipopolysaccharides; D043885:Receptor, Cannabinoid, CB2; D007371:Interferon-gamma; C016299:chelerythrine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011493:Protein Kinase C; C544448:Arg1 protein, mouse; D001119:Arginase; C094023:iodopravadoline
keywords: Cannabinoid CB2 receptor; Inflammation; Microglia; Pretreatment; Protein kinase C