BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation

  • Kim, Su Min (Department of Biomedical Laboratory Science, Konyang University) ;
  • Ha, Ji Sun (Department of Biomedical Laboratory Science, Konyang University) ;
  • Han, A Reum (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University)
  • Received : 2019.01.25
  • Accepted : 2019.02.12
  • Published : 2019.10.31
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Abstract

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.

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References

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