Original Article

A novel synthetic compound MCAP suppresses LPSinduced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways

Authors: Byung-Wook KIM, Sandeep Vasant MORE, Yo-Sep YUN, Hyun-Myung KO, Jae-Hwan KWAK, Heesoon LEE, Kyoungho SUK, In-Su KIM, Dong-Kug CHOI
DOI: 10.1038/aps.2015.138


Aim: 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).
Conclusion: 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.
Keywords: 7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl) phenylamide (MCAP); microglia; NO; NF-κB; MAPKs; LPS; SB203580; neuroinflammation

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