High-dose wogonin exacerbates DSS-induced colitis by up-regulating effector T cell function and inhibiting Treg cell

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• 作者：Weiming Xiao ; Min Yin ; Keyan Wu ; Guotao Lu ; Bin Deng ; Yu Zhang ; Li Qian ; Xiaoqing Jia ; Yanbing Ding and Weijuan Gong
• 刊名：Journal of Cellular and Molecular Medicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：21
• 期：2
• 页码：286-298
• 全文大小：1602K
• ISSN：1582-4934

文摘

Wogonin exerts anti-tumour activities via multiple mechanisms. We have identified that high-dose wogonin (50 or 100 mg/kg) could inhibit the growth of transplanted tumours by directly inducing tumour apoptosis and promoting DC, T and NK cell recruitment into tumour tissues to enhance immune surveillance. However, wogonin (20&ndash;50 μM) ex vivo prevents inflammation by inhibiting NF-κB and Erk signalling of macrophages and epithelial cells. It is elusive whether high-dose wogonin promotes or prevents inflammation. To investigate the effects of high-dose wogonin on murine colitis induced by dextran sodium sulphate (DSS), mice were co-treated with DSS and various doses of wogonin. Intraperitoneal administration of wogonin (100 mg/kg) exacerbated DSS-induced murine colitis. More CD4<sup>+sup> CD44<sup>+sup> and CD8<sup>+sup> CD44<sup>+sup> cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4<sup>+sup> CD25<sup>+sup> CD127<sup>&minus;sup> and CD4<sup>+sup> CD25<sup>+sup> Foxp3<sup>+sup> cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high-dose wogonin (50&ndash;100 μg/ml equivalent to 176&ndash;352 μM) could synergize with IL-2 to promote the functions of CD4<sup>+sup> and CD8<sup>+sup> cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF-κB and Erk but down-regulated STAT3 phosphorylation in the CD4<sup>+sup> T cells. Wogonin down-regulated Erk and STAT3-Y705 phosphorylation in the regulatory T cells but promoted NF-κB and STAT3-S727 activation. Our study demonstrated that high-dose wogonin treatments would enhance immune activity by stimulating the effector T cells and by down-regulating regulatory T cells.