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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 35, Number 11
BKCSDE 35(11)
November 20, 2014 

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
Hyun Jung Park, Sung Won Lee, Hwangseo Park, Se-Ho Park*, Seokmann Hong*
Tubulin inhibitor, N-(5-Benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide, Anticancer, Anti-inflammatory, Sepsis
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 (IFNγ) induced by LPS treatment. Moreover, 1 substantially reduced interleukin 12 in dendritic cells (DC) as well as IFNγ 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 LPSinduced innate immune responses. Therefore, 1 might have therapeutic potential for the treatment of inflammation-mediated diseases such as sepsis.
3307 - 3312
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