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Anti-inflammatory Effects of Metformin on Neuro-inflammation and NLRP3 Inflammasome Activation in BV-2 Microglial Cells
Biomed Sci Letters 2019;25:92-98
Published online March 31, 2019;  https://doi.org/10.15616/BSL.2019.25.1.92
© 2019 The Korean Society For Biomedical Laboratory Sciences.

Ji-Sun Ha1,*, Yun-Seon Yeom1,**, Ju-Hun Jang1,**, Yong-Hee Kim1,**, Ji In Im1,**, In Sik Kim2,*** and Seung-Ju Yang1,,***

1Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea 2Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Korea
Correspondence to: Seung-Ju Yang. Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea.
Tel: +82-10-7373-5922, Fax: +82-10-7373-5922, e-mail: sjyang@konyang.ac.kr
Received February 28, 2019; Revised March 21, 2019; Accepted March 22, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-慣 and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.
Keywords : Autophagy, Metformin, Microglia, NLRP3 inflammasome