Open AccessHigh‐dose wogonin exacerbates DSS ‐induced colitis by up‐regulating effector T cell function and inhibiting Treg cell
Author(s) -
Xiao Weiming,
Yin Min,
Wu Keyan,
Lu Guotao,
Deng Bin,
Zhang Yu,
Qian Li,
Jia Xiaoqing,
Ding Yanbing,
Gong Weijuan
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12964
Subject(s) - wogonin , foxp3 , mapk/erk pathway , cell growth , chemistry , pharmacology , inflammation , immune system , immunology , cancer research , phosphorylation , medicine , scutellaria baicalensis , biochemistry , pathology , alternative medicine , traditional chinese medicine
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 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 CD 4 + CD 44 + and CD 8 + CD 44 + cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD 4 + CD 25 + CD 127 − and CD 4 + CD 25 + Foxp3 + cells in the colons and spleen respectively, were reduced by wogonin treatment. Ex vivo stimulations with high‐dose wogonin (50–100 μg/ml equivalent to 176–352 μM) could synergize with IL ‐2 to promote the functions of CD 4 + and CD 8 + cells. However, regulatory T cell induction was inhibited. Wogonin stimulated the activation of NF ‐κB and Erk but down‐regulated STAT 3 phosphorylation in the CD 4 + T cells. Wogonin down‐regulated Erk and STAT 3‐Y705 phosphorylation in the regulatory T cells but promoted NF ‐κB and STAT 3‐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.