数字农科院2.0

Tizoxanide Inhibits Inflammation In Lps-Activated R.aw264.7 Macrophages Via The S uppression Of Nf-Kappa B And Mapk Activation

文献类型： 外文期刊

作者： Shou, JQ; Kong, XZ; Wang, XY; Tang, Y; Wang, CM; Wang, M; Zhang, LF; Liu, YC; Fei, CZ; Xue, FQ; Li, J; Zhang, KY

作者机构：

关键词： tizoxanide; RAW264; 7 cells; lipopolysaccharide; anti-inflammation; NF-kappa B; MAPKs

期刊名称： INFLAMMATION

ISSN： 0360-3997

年卷期： 2019 年 42 卷 4 期

页码：

收录情况： JCR（2021版）

摘要： Tizoxanide is the main active metabolite of nitazoxanide. Nitazoxanide and tizoxanide have a broad-spectrum anti-infective effect, including parasites, bacteria, and virus. In the present study, we investigated the anti-inflammatory effect of tizoxanide on lipopolysaccharide (LPS)-stimulated RAW264.7 cells and revealed underlying molecular mechanisms. The results showed that tizoxanide significantly suppressed production of NO as well as pro-inflammatory cytokines, such as IL-1 beta, IL-6, and TNF-alpha in dose-dependent manner. Meanwhile, the levels of gene expression of these cytokines were inhibited significantly by tizoxanide that was discovered using RT-PCR. The increased protein levels of inducible nitric oxide synthase, heme oxygenase-1, and cyclooxygenase-2 by LPS in the cells were also reduced by tizoxanide. Moreover, we found that tizoxanide inhibited the phosphorylation of IKK-alpha and degradation of I kappa B by LPS in macrophage cells. The increased protein levels of p65 induced by LPS in the cytoplasm and nucleus were both decreased by tizoxanide, and the nuclear translocation of p65 was also restrained in cell imaging. In addition, tizoxanide considerably also inhibited LPS-activated JNK, p38, and ERK phosphorylation in RAW264.7 cells. Taken together, our results suggested that tizoxanide exerts anti-inflammatory effects, by inhibiting the production of pro-inflammatory cytokines and suppressing of the activation of the NF-kappa B and the MAPK signaling pathways in LPS-treated macrophage cells.

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