Korean Circ J.  2005 Aug;35(8):576-582. 10.4070/kcj.2005.35.8.576.

Carvedilol Inhibits Expressions of Vascular Cell Adhesion Molecule-1, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant-1, and Interleukin-8 via NF-kappaB Inhibition in Human Endothelial Cells

• Kim YS
• Ahn Y
• Hong MH
• Joo SY
• Jeong MH
• Kim KH
• Sohn IS
• Park HW
• Hong YJ
• Kim JH
• Kim W
• Cho JG
• Park JC
• Kang JC

• KMID: 2093943
• DOI: http://doi.org/10.4070/kcj.2005.35.8.576

Abstract

BACKGROUND AND OBJECTIVES
Carvedilol is an anti-oxidative, the cardioprotective effects of which are mediated by the inhibition of NF-kappaB activation. The present study was designed to examine the effects of carvedilol, an alpha1- and beta-blocker, on tumor necrosis factor (TNF)-alpha stimulated human umbilical vein endothelial cells (HUVEC). Materials and
METHODS
HUVEC were treated with TNF-alpha (10 ng/mL) in either the absence or presence of carvedilol. The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, with the adhesion of U-937 monocyte to the HUVEC. Nuclear factor kappa B (NF-kappaB) activation was determined by NF-kappaB p65 translocation to the nucleus using Western blotting and immunocytochemistry. The expressions of NF-kappaB dependent pro-inflammatory molecules, i.e., vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, were measured by RT-PCR and ELISA. Bcl-2 and phosphorylation of c-Jun N-terminal protein kinase (JNK) were measured using Western blotting.
RESULTS
TNF-alpha treatment increased the activation of NF-kappaB, suppressed Bcl-2, and increased the phosphorylation of JNK, the ROS level and the adhesion of U-937. The levels of mRNA and protein expressions of VCAM-1, ICAM-1, MCP-1 and IL-8 were up-regulated by TNF-alpha. Carvedilol inhibited the phosphorylation of JNK, ROS formation and the adhesion of U-937 monocyte. In addition, carvedilol reduced the production of VCAM-1, ICAM-1, MCP-1 and IL-8 at the mRNA and protein levels, via the suppression of NF-kappaB activation.
CONCLUSION
These results suggested that the anti-inflammatory effects of carvedilol on TNF-alpha stimulated endothelial cells could be explained by its ROS-scavenging and NF-kappaB inactivation properties.

Keyword

Carvedilol; Tumor necrosis factor-alpha, nuclear factor-kappaB, endothelial cell

MeSH Terms

Blotting, Western
Endothelial Cells*
Enzyme-Linked Immunosorbent Assay
Human Umbilical Vein Endothelial Cells
Humans*
Immunohistochemistry
Intercellular Adhesion Molecule-1*
Interleukin-8*
Interleukins
Monocytes*
NF-kappa B*
Phosphorylation
Protein Kinases
Reactive Oxygen Species
RNA, Messenger
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1*
Intercellular Adhesion Molecule-1
Interleukin-8
Interleukins
NF-kappa B
Protein Kinases
RNA, Messenger
Reactive Oxygen Species
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1