期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 21, 期 2, 页码 286-298出版社
WILEY
DOI: 10.1111/jcmm.12964
关键词
wogonin; exacerbate; colitis; effector T cell; regulatory T cell
资金
- National Natural Science Foundation [81471547, 81273214, 81172785]
- Natural Science Fund of Jiangsu Province [BK2011449, BK2008215]
- Yangzhou University
- Yangzhou Municipality [2012038-5]
- Social Development Fund of Yangzhou Municipality [YZ2014179]
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 (20-50 M) ex vivo prevents inflammation by inhibiting NF-B 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(+) CD44(+) and CD8(+) CD44(+) cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4(+) CD25(+) CD127(-) and CD4(+) CD25(+) Foxp3(+) cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high-dose wogonin (50-100 g/ml equivalent to 176-352 M) could synergize with IL-2 to promote the functions of CD4(+) and CD8(+) cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF-B and Erk but down-regulated STAT3 phosphorylation in the CD4(+) T cells. Wogonin down-regulated Erk and STAT3-Y705 phosphorylation in the regulatory T cells but promoted NF-B 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.
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