title: Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to β Amyloid via Protein Kinase C.
abstract: BACKGROUND
  Reducing β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process.
  
  
  METHODS
  We used Aβ1-42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor α (TNF-α) and interleukin- (IL-) 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1) expression and brain-derived neurotrophic factor (BDNF) release, in the Aβ-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC) inhibitor partially abolished the nicotine-induced effects.
  
  
  CONCLUSIONS
  These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Aβ via PKC.
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Zhaoju
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Youping
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Qunlin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Anesthesiology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Wu
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D043885:Receptor, Cannabinoid, CB2; D009538:Nicotine; D011493:Protein Kinase C