Carvedilol, a new antioxidative beta-blocker, blocks in vitro human peripheral blood T cell activation by
Shih-Ping Yang1, Ling-Jun Ho, Yi-Ling Lin
1Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Objective:
The activation of T lymphocytes contributes to the inflammatory process of atherosclerosis. Here we examined the effects of carvedilol, a new beta-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-kappaB and related protein activity was determined by electrophoretic mobility shift assays, Western blotting, kinase assays and transfection assays.
Results:
Carvedilol was nontoxic at concentrations /=20 microM) 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-kappaB 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 IkappaBalpha degradation. Such an effect was mediated through the inhibition of IkappaBalpha kinase activity. The inhibitory specificity on NF-kappaB 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-kappaB activity.
Insights
Carvedilol, an antioxidant beta-blocker, inhibits T cell activation by downregulating NF-kappaB. This reveals a new therapeutic approach for atherosclerosis by targeting inflammatory T cells.
Area of Science:
- Immunology
- Cardiovascular Research
- Pharmacology
Background:
- T lymphocyte activation is crucial in atherosclerosis pathogenesis.
- Carvedilol possesses both beta-blocking and antioxidant properties.
Purpose of the Study:
- To investigate the effects of carvedilol on T cell activation.
- To explore carvedilol's potential therapeutic mechanism in atherosclerosis.
Main Methods:
- Human peripheral blood T cells were isolated.
- Cytokine production, T cell activation markers (CD25, CD69, CD71), and NF-kappaB activity were assessed using ELISA, Western blotting, and electrophoretic mobility shift assays.
Main Results:
- Carvedilol (
- Carvedilol inhibited cytokine production and T cell activation markers.
- Carvedilol specifically downregulated NF-kappaB activity by inhibiting IkappaBalpha kinase, likely via its antioxidant effects.
Conclusions:
- Carvedilol inhibits T cell activation through NF-kappaB downregulation.
- This presents a novel therapeutic mechanism for carvedilol in treating atherosclerosis.
Related Concept Videos
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
01:17Antihypertensive Drugs: Action of β1 Blockers
01:18Antihypertensive Drugs: Action of Calcium Channel Blockers
01:24Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:28Antihypertensive Drugs: Types of β-Blockers