Abstract |
Facilitating T-cell apoptosis is implicated as an effective therapeutic strategy for treatment of T cell-mediated disease, including inflammatory bowel disease. Here, we report that astin C, a plant cyclopeptide isolated from the roots of Aster tataricus (Compositae), induced apoptosis of activated T cells in a mitochondria-dependent but Fas-independent manner in that such activity was still observed in T cells from Fas-mutated MRLlpr/lpr mice. Although caspase 8 was not activated, astin C treatment led to the cleavage of caspase 9 and caspase 3, the upregulation of Bad protein expression as well as release of cytochrome c in activated T cells. Astin C did not induce the expression of GRP78 and GADD153, excluding involvement of endoplasmic reticulum stress-mediated pathway. Moreover, oral administration of astin C protected mice against TNBS-induced colonic inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Administering astin C significantly decreased serum levels of TNF-α, IL-4 and IL-17, accompanied with the induction of apoptosis in activated T cells in vivo. The results demonstrate, for the first time, the ability of astin C to induce apoptosis in activated T cells and its potential use in the treatment of colonic inflammation.
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Authors | Yan Shen, Qiong Luo, Huimin Xu, Fangyuan Gong, Xiaobin Zhou, Yang Sun, Xuefeng Wu, Wen Liu, Guangzhi Zeng, Ninghua Tan, Qiang Xu |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 82
Issue 3
Pg. 260-8
(Aug 01 2011)
ISSN: 1873-2968 [Electronic] England |
PMID | 21569765
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents
- Cytokines
- Endoplasmic Reticulum Chaperone BiP
- Hspa5 protein, mouse
- Peptides, Cyclic
- astin C
- Trinitrobenzenesulfonic Acid
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Topics |
- Animals
- Anti-Inflammatory Agents
(chemistry, pharmacology)
- Apoptosis
(drug effects, physiology)
- Aster Plant
(chemistry)
- Cells, Cultured
- Colitis
(chemically induced, prevention & control)
- Cytokines
(genetics, metabolism)
- Endoplasmic Reticulum Chaperone BiP
- Female
- Gene Expression Regulation
(drug effects)
- Mice
- Mice, Inbred C57BL
- Mitochondria
(metabolism)
- Peptides, Cyclic
(chemistry, pharmacology)
- Plant Roots
(chemistry)
- T-Lymphocytes
(drug effects, physiology)
- Trinitrobenzenesulfonic Acid
(toxicity)
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