Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6074504 | Journal of Investigative Dermatology | 2016 | 35 Pages |
Abstract
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.
Keywords
ACDrps3p27KipPhosphorylated protein kinase Bphosphorylated signal transducer and activator of transcriptionConAPCLCCCPLC3Concanavalin Ap-AktSTATCSAACD, Allergic contact dermatitisCyclosporine ASignal transducer and activator of transcriptionretinoblastoma proteinmicrotubule-associated protein 1 light chain 3carbonyl cyanide m-chlorophenylhydrazoneChloroquine
Related Topics
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Medicine and Dentistry
Dermatology
Authors
Xingqi Wang, Chunhui Hu, Xingxin Wu, Shiyu Wang, Aihua Zhang, Wei Chen, Yan Shen, Renxiang Tan, Xuefeng Wu, Yang Sun, Qiang Xu,