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KMID : 1144820190250010092
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대한의생명과학회지
2019 Volume.25 No. 1 p.92 ~ p.98
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Anti-inflammatory Effects of Metformin on Neuro-inflammation and NLRP3 Inflammasome Activation in BV-2 Microglial Cells
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Ha Ji-Sun
Yeom Yun-Seon
Jang Ju-Hun
Kim Yong-Hee
Im Ji-In
Kim In-Sik
Yang Seung-Ju
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Abstract
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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-α 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.
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KEYWORD
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Autophagy, Metformin, Microglia, NLRP3 inflammasome
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