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Cardiovascular Research 2003 59(3):776-787; doi:10.1016/S0008-6363(03)00459-0
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Carvedilol, a new antioxidative β-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-{kappa}B activity

Shih-Ping Yanga,1, Ling-Jun Hob,1, Yi-Ling Linb, Shu-Meng Chenga, Tien-Ping Tsaoa, Deh-Ming Changc, Yu-Lin Hsuc, Chin-Yi Shihc, Ting-Yi Juanc and Jenn-Haung Laic,*

aCardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
bInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC
cRheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Kung Rd., Neihu 114, Taipei, Taiwan, ROC

haungben{at}tpts5.seed.net.tw

* Corresponding author. Tel.: +886-2-8792-7135; fax: +886-2-8792-7136.

Objective: The activation of T lymphocytes contributes to the inflammatory process of atherosclerosis. Here we examined the effects of carvedilol, a new β-blocker containing an antioxidative property, on the activation of T cells. Methods: Human peripheral blood T cells were negatively selected from whole blood. Cytokines were measured by ELISA. The NF-{kappa}B and related protein activity was determined by electrophoretic mobility shift assays, Western blotting, kinase assays and transfection assays. Results: Carvedilol was nontoxic at concentrations less double equals10 µM, however, higher dosages (≥20 µM) induced T cell apoptosis. We demonstrated that carvedilol inhibited cytokine production from various stimuli-activated T cells. Carvedilol also suppressed the expression of T cell activation markers, including CD25, CD69 and CD71. Molecular investigation indicated that carvedilol specifically downregulated NF-{kappa}B but not activator protein 1 DNA-binding activity in activated T cells. The inhibitory effect was likely due to its antioxidative property. Meanwhile, carvedilol prevented stimuli-induced I{kappa}B{alpha} degradation. Such an effect was mediated through the inhibition of I{kappa}B{alpha} kinase activity. The inhibitory specificity on NF-{kappa}B by carvedilol was also demonstrated in transfection assays. Conclusions: Our results demonstrated a novel therapeutic mechanism of carvedilol in atherosclerosis, namely the inhibition of T cell activation via downregulating NF-{kappa}B activity.

KEYWORDS Carvedilol; Atherosclerosis; T cells; Cytokines; NF-{kappa}B

1 S.-P. Yang and L.-J. Ho contributed equally to this work.


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