title: High-dose wogonin exacerbates DSS-induced colitis by up-regulating effector T cell function and inhibiting Treg cell.
abstract: 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 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 μg/ml equivalent to 176-352 μM) 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-κB 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-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.
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Keyan
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Guotao
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.affiliation: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Affiliated hospital, Yangzhou University, Yangzhou, China.|Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.|Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.|Jiangsu Key Laboratory of Zoonosis, Yangzhou, China.|Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.|Key Research Laboratory of Theory and Treatment on Toxicity of Stomach Cancer, State Administration of Traditional Chinese Medicine, Yangzhou, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gong
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D016264:Dextran Sulfate; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044950:Flavanones / Q000009:adverse effects*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D044950:Flavanones; D007376:Interleukin-2; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D016264:Dextran Sulfate; D048049:Extracellular Signal-Regulated MAP Kinases; C085514:wogonin
keywords: colitis; effector T cell; exacerbate; regulatory T cell; wogonin