Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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A Tubulin Inhibitor, N-(5-Benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide, Induces Anti-inflammatory Innate Immune Responses to Attenuate LPS-mediated Septic Shock

  • Park, Hyun Jung (Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University) ;
  • Lee, Sung Won (Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University) ;
  • Park, Hwangseo (Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University) ;
  • Park, Se-Ho (Department of Life Sciences, Korea University) ;
  • Hong, Seokmann (Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University)
  • Received : 2014.06.26
  • Accepted : 2014.07.31
  • Published : 2014.11.20
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Abstract

The anti-inflammatory effect of a tubulin inhibitor, N-(5-benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide (1), on innate immune responses remains unclear. Thus, we investigated the effect of 1 on the immune responses mediated by lipopolysaccharide (LPS). The in vitro addition of 1 to dendritic cells and macrophages dose-dependently reduced tumor necrosis factor alpha production elicited by LPS stimulation. Additionally, the stimulation of natural killer (NK) and natural killer T (NKT) cells with 1 resulted in the decrease of interferon gamma ($IFN{\gamma}$) induced by LPS treatment. Moreover, 1 substantially reduced interleukin 12 in dendritic cells (DC) as well as $IFN{\gamma}$ in NKDCs induced by LPS in vitro. Furthermore, the in vivo administration of 1 ameliorated LPS/D-galactosamine-induced endotoxic lethality in mice. Taken together, our results demonstrate for the first time that 1 possesses anti-inflammatory properties, most notably by modulating LPS-induced innate immune responses. Therefore, 1 might have therapeutic potential for the treatment of inflammation-mediated diseases such as sepsis.

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