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

Bulletin of the Korean chemical society

Hwangseo Park¹  Seokmann Hong¹  Sung Won Lee¹  Hyun Jung Park¹  Se-Ho Park¹ 

关键词: Tubulin inhibitor;    N-(5-Benzyl-1;    3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide;    Anticancer;    Anti-inflammatory;    Sepsis;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

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.

【 授权许可】

Unknown