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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Anti-inflammatory effects of N-cyclooctyl-5-methylthiazol-2-amine hydrobromide on lipopolysaccharide-induced inflammatory response through attenuation of NLRP3 activation in microglial cells

  • Kim, Eun-A (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Hwang, Kyouk (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Kim, Ji-Eun (Department of Biomedical Laboratory Science, Konyang University) ;
  • Ahn, Jee-Yin (Department of Molecular Cell Biology and Single Cell Network Research Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University) ;
  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, Konyang University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine)
  • Received : 2021.06.28
  • Accepted : 2021.07.22
  • Published : 2021.11.30
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Abstract

Microglial activation is closely associated with neuroinflammatory pathologies. The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasomes are highly organized intracellular sensors of neuronal alarm signaling. NLRP3 inflammasomes activate nuclear factor kappa-B (NF-κB) and reactive oxygen species (ROS), which induce inflammatory responses. Moreover, NLRP3 dysfunction is a common feature of chronic inflammatory diseases. The present study investigated the effect of a novel thiazol derivative, N-cyclooctyl-5-methylthiazol-2-amine hydrobromide (KHG26700), on inflammatory responses in lipopolysaccharide (LPS)-treated BV-2 microglial cells. KHG26700 significantly attenuated the expression of several pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, in these cells, as well as the LPS-induced increases in NLRP3, NF-κB, and phospho-IkBα levels. KHG26700 also suppressed the LPS-induced increases in protein levels of autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 (LC3), and beclin-1, as well as downregulating the LPS-enhanced levels of ROS, lipid peroxidation, and nitric oxide. These results suggest that the anti-inflammatory effects of KHG26700 may be due, at least in part, to the regulation of the NLRP3-mediated signaling pathway during microglial activation.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2018R1A2B6001743 and 2021R1F1A1051920), and by a Student Research Grant from the University of Ulsan College of Medicine, Seoul, Korea.

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