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Carvedilol, a new antioxidative β-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-κB activity
- Source :
- Cardiovascular Research; Sep2003, Vol. 59 Issue 3, p776, 12p
- Publication Year :
- 2003
-
Abstract
- <B>Objective:</B> 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. <B>Methods:</B> Human peripheral blood T cells were negatively selected from whole blood. Cytokines were measured by ELISA. The NF-κB and related protein activity was determined by electrophoretic mobility shift assays, Western blotting, kinase assays and transfection assays. <B>Results:</B> Carvedilol was nontoxic at concentrations ≦10 μM, however, higher dosages (&ges;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-κB 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 IκBα degradation. Such an effect was mediated through the inhibition of IκBα kinase activity. The inhibitory specificity on NF-κB by carvedilol was also demonstrated in transfection assays. <B>Conclusions:</B> Our results demonstrated a novel therapeutic mechanism of carvedilol in atherosclerosis, namely the inhibition of T cell activation via downregulating NF-κB activity. [Copyright &y& Elsevier]
- Subjects :
- NF-kappa B
ATHEROSCLEROSIS
T cells
Subjects
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 59
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 10807442
- Full Text :
- https://doi.org/10.1016/S0008-6363(03)00459-0