title: Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone.
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-κB) DNA-binding activities in activated human T cells and also inhibited DNA binding and transcriptional activities of both AP-1 and NF-κB in Jurkat cells. Finally, by Western blotting, we showed that amiodarone reduced the activation of c-Jun NH(2)-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-κB 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.
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C.
authors: Shu-Meng
authors: SM
authors: Cheng
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C.
authors: Wei-Hsiang
authors: WH
authors: Lin
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C.
authors: Chin-Sheng
authors: CS
authors: Lin
authors: Institute of Cellular and System Medicine, National Health Research Institute, Zhunan 350, Taiwan, R.O.C.
authors: Ling-Jun
authors: LJ
authors: Ho
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C.
authors: Tsung-Neng
authors: TN
authors: Tsai
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C.
authors: Chun-Hsien
authors: CH
authors: Wu
authors: Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan 333, Taiwan, R.O.C.
authors: Jenn-Haung
authors: JH
authors: Lai
authors: Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114, Taiwan, R.O.C spjyang@ms12.hinet.net.
authors: Shih-Ping
authors: SP
authors: Yang
mesh_terms: D000328:Adult; D000638:Amiodarone / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D064368:Healthy Volunteers; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D000638:Amiodarone
keywords: Amiodarone; T cells; activator protein-1; cytokine; nuclear factor kappa-B