Roseotoxin B Improves Allergic Contact Dermatitis through a Unique Anti-Inflammatory Mechanism Involving Excessive Activation of Autophagy in Activated T Lymphocytes
2016-12-21 18:51发表评论
作者:Wang, X., Hu, C., Wu, X., Wang, S., Zhang, A., Chen, W., Shen, Y., Tan, R., Wu, X.a, Sun, Y., Xu, Q
机构: 南京大学生命科学院,医药生物技术国家重点实验室
期刊: J Invest Dermatol2016年8月8期136卷

An immunosuppressant agent with negligible or acceptable toxicity may provide a better therapeutic strategy for treatment of allergic contact dermatitis. We identified a natural cyclopeptide, roseotoxin B, that effectively suppressed cell proliferation and the production of proinflammatory cytokines in activated T cells but exhibited little naive T-cell toxicity at concentrations of 0.3–1 μmol/L. In addition, roseotoxin B inhibited the activation of AKT and signal transducer and activator of transcription-3, suppressed cell cycle-related signaling, caused G0/G1 phase arrest, reduced ribosomal protein-S3 (RPS3)–dependent NF-κB–mediated IL-2 production, and increased autophagy in activated T cells. Furthermore, picryl chloride-induced allergic contact dermatitis was significantly ameliorated by roseotoxin B in mice. The effects of roseotoxin B were inhibited in LC3-knockout mice, indicating that roseotoxin B acts in an autophagy-dependent manner in T-cell–mediated skin diseases. Overall, this study showed a mechanism for roseotoxin B-induced autophagic cell death and provided a unique perspective on autophagy-mediated down-regulation of NF-κB signaling in activated T cells. The unique anti-inflammatory mechanism of roseotoxin B against activated T lymphocytes in allergic contact dermatitis suggests that it could be a potential target for the treatment of immune-related skin diseases. © 2016 The Authors

通讯机构:State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
学科代码:基础医学 皮肤病学   关键词:RoseotoxinB通过涉及活化性T淋巴细胞自噬过度活化在 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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