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High-dose wogonin exacerbates DSS-induced colitis by up-regulating effector T cell function and inhibiting Treg cell.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2017 Feb; Vol. 21 (2), pp. 286-298. Date of Electronic Publication: 2016 Sep 19. - Publication Year :
- 2017
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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 <superscript>+</superscript> CD44 <superscript>+</superscript> and CD8 <superscript>+</superscript> CD44 <superscript>+</superscript> cells were located in the inflamed colons in the wogonin (100 mg/kg) treatment group than in the other groups. Frequencies of CD4 <superscript>+</superscript> CD25 <superscript>+</superscript> CD127 <superscript>-</superscript> and CD4 <superscript>+</superscript> CD25 <superscript>+</superscript> Foxp3 <superscript>+</superscript> 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 <superscript>+</superscript> and CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Animals
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
Cell Line, Tumor
Colitis pathology
Dextran Sulfate
Down-Regulation drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Interleukin-2 pharmacology
Lymphocyte Activation drug effects
Lymphocyte Activation immunology
Lymphocyte Count
Mice, Inbred C57BL
NF-kappa B metabolism
Phosphorylation drug effects
STAT3 Transcription Factor metabolism
T-Lymphocytes, Regulatory drug effects
Up-Regulation drug effects
Colitis chemically induced
Colitis immunology
Disease Progression
Flavanones adverse effects
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 27641629
- Full Text :
- https://doi.org/10.1111/jcmm.12964