PMID- 26884647 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181113 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2016 DP - 2016 TI - Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to beta Amyloid via Protein Kinase C. PG - 4854378 LID - 10.1155/2016/4854378 [doi] LID - 4854378 AB - BACKGROUND: Reducing beta amyloid- (Abeta-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Abeta-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 Abeta-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. METHODS: We used Abeta1-42 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 alpha (TNF-alpha) 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 Abeta-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC) inhibitor partially abolished the nicotine-induced effects. CONCLUSION: These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti-inflammation in microglia exposed to Abeta via PKC. FAU - Jia, Ji AU - Jia J AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Peng, Jie AU - Peng J AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Li, Zhaoju AU - Li Z AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Wu, Youping AU - Wu Y AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Wu, Qunlin AU - Wu Q AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Tu, Weifeng AU - Tu W AD - Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China. FAU - Wu, Mingchun AU - Wu M AD - Department of Anesthesiology, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160113 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Amyloid beta-Peptides) RN - 0 (Receptor, Cannabinoid, CB2) RN - 6M3C89ZY6R (Nicotine) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - Amyloid beta-Peptides/*pharmacology MH - Animals MH - Cell Line MH - Inflammation/*metabolism MH - Mice MH - Microglia/*drug effects/immunology/*metabolism MH - Nicotine/*pharmacology MH - Protein Kinase C/*metabolism MH - Receptor, Cannabinoid, CB2/*metabolism PMC - PMC4738711 EDAT- 2016/02/18 06:00 MHDA- 2016/12/15 06:00 PMCR- 2016/01/13 CRDT- 2016/02/18 06:00 PHST- 2015/10/17 00:00 [received] PHST- 2015/12/07 00:00 [revised] PHST- 2015/12/16 00:00 [accepted] PHST- 2016/02/18 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2016/01/13 00:00 [pmc-release] AID - 10.1155/2016/4854378 [doi] PST - ppublish SO - Mediators Inflamm. 2016;2016:4854378. doi: 10.1155/2016/4854378. Epub 2016 Jan 13.