title: A novel synthetic compound MCAP suppresses LPS-induced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways.
abstract: OBJECTIVE
  To investigate the anti-neuroinflammatory activity of a novel synthetic compound, 7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl) phenylamide (MCAP) against LPS-induced microglial activation in vitro.
  
  
  METHODS
  Primary mouse microglia and BV2 microglia cells were exposed to LPS (50 or 100 ng/mL). The expression of iNOS and COX-2, proinflammatory cytokines, NF-κB and p38 MAPK signaling molecules were analyzed by RT-PCR, Western blot and ELISA. The morphological changes of microglia and nuclear translocation of NF-ĸB were visualized using phase contrast and fluorescence microscopy, respectively.
  
  
  RESULTS
  Pretreatment with MCAP (0.1, 1, 10 μmol/L) dose-dependently inhibited LPS-induced expression of iNOS and COX-2 in BV2 microglia cells. Similar results were obtained in primary microglia pretreated with MCAP (0.1, 0.5 μmol/L). MCAP dose-dependently abated LPS-induced release of TNF-α, IL-6 and IL-1β, and mitigated LPS-induced activation of NF-κB by reducing the phosphorylation of IκBα in BV2 microglia cells. Moreover, MCAP attenuated LPS-induced phosphorylation of p38 MAPK, whereas SB203580, a p38 MAPK inhibitor, significantly potentiated MCAP-caused inhibition on the expression of MEF-2 (a transcription factor downstream of p38 MAPK).
  
  
  CONCLUSIONS
  MCAP exerts anti-inflammatory effects in murine microglia in vitro by inhibiting the p38 MAPK and NF-κB signaling pathways and proinflammatory responses. MCAP may be developed as a novel agent for treating diseases involving activated microglial cells.
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.|Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Byung-Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Sandeep Vasant
authors.initials: SV
authors.lastname: More
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Yo-Sep
authors.initials: YS
authors.lastname: Yun
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Hyun-Myung
authors.initials: HM
authors.lastname: Ko
authors.affiliation: College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea.
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea.
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Dong-Kug
authors.initials: DK
authors.lastname: Choi
mesh_terms: D000813:Anilides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: C000613309:7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl)phenylamide; D000813:Anilides; D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases
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