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http://ir.nhri.org.tw/handle/3990099045/8183
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| Title: | Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone |
| Authors: | Cheng, SM;Lin, WH;Lin, CS;Ho, LJ;Tsai, TN;Wu, CH;Lai, JH;Yang, SP |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | Amiodarone, a common and effective antiarrhythmic drug, has been reported to have anti-inflammatory effects such as reducing the activation and movement of neutrophils. However, its effects on human T cells remain unclear. The aim of this study was to elucidate the effects and possible underlying mechanisms of amiodarone on human T cells. We isolated human primary T cells from the peripheral blood of healthy volunteers and performed enzyme-linked immunosorbent assay (ELISA), flow cytometry, electrophoretic mobility shift assay, luciferase assay, and Western blotting to evaluate the modulatory effects of amiodarone on human T cells. We found that amiodarone dose dependently inhibited the production of cytokines, including interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha, and interferon-gamma in activated human T cells. By flow cytometry, we demonstrated that amiodarone suppressed the expression of IL-2 receptor-alpha (CD25) and CD69, the cell surface markers of activated T cells. Moreover, molecular investigations revealed that amiodarone down-regulated activator protein-1 (AP-1) and nuclear factor kappa-B (NF-kappaB) DNA-binding activities in activated human T cells and also inhibited DNA binding and transcriptional activities of both AP-1 and NF-kappaB in Jurkat cells. Finally, by Western blotting, we showed that amiodarone reduced the activation of c-Jun NH2-terminal protein kinase and P38 mitogen-activated protein kinase, and suppressed stimuli-induced I-kappa B-alpha degradation in activated human T cells. Through regulation of AP-1 and NF-kappaB signaling, amiodarone inhibits cytokine production and T cell activation. These results show the pleiotropic effects of amiodarone on human T cells and suggest its therapeutic potential in inflammation-related cardiovascular disorders. |
| Date: | 2015-01 |
| Relation: | Experimental Biology and Medicine. 2015 Jan;240(1):99-108. |
| Link to: | http://dx.doi.org/10.1177/1535370214544263 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-3702&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000347977400011 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84920996425 |
| Appears in Collections: | [何令君] 期刊論文
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| PUB25073960.pdf | | 539Kb | Adobe PDF | 576 | View/Open |
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