title: Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis.
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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
authors.forename: Huimin
authors.initials: H
authors.lastname: Xu
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Gong
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Zeng
authors.forename: Ninghua
authors.initials: N
authors.lastname: Tan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D031173:Aster Plant / Q000737:chemistry; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D010456:Peptides, Cyclic; C096028:astin C; D014302:Trinitrobenzenesulfonic Acid