pISSN 1226-4512 eISSN 2093-3827

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Korean J Physiol Pharmacol 2006; 10(4): 217-221

Published online August 30, 2006

Copyright © Korean J Physiol Pharmacol.

NADPH Oxidase and Mitochondrial ROS are Involved in the TNF-α-induced Vascular Cell Adhesion Molecule-1 and Monocyte Adhesion in Cultured Endothelial Cells

Jae Hyeon Yu1*, Cuk Seong Kim2*, Dae Goon Yoo2, Yun Jeong Song2, Hee Kyoung Joo2, Gun Kang2, Ji Yoon Jo2, Jin Bong Park2, and Byeong Hwa Jeon2

Departments of 1Thoracic Surgery, 2Physiology, College of Medicine, Chungnam National University, Daejeon 301-131, Korea

Abstract

Atherosclerosis is considered as a chronic inflammatory process. However, the nature of the oxidant signaling that regulates monocyte adhesion and its underlying mechanism is poorly understood. We investigated the role of reactive oxygen species on the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion in the cultured endothelial cells. TNF-α at a range of 1~30 ng/ml induced VCAM-1 expression dose-dependently. BCECF-AM-labeled U937 cells firmly adhered on the surface of endothelial cells when the endothelial cells were incubated with TNF-α (15 ng/ml). Ten μmol/L of SB203580, an inhibitor of p38 MAPK, significantly reduced TNF-α-induced VCAM-1 expression, compared to the JNK inhibitor (40μmol/L of SP60015) or ERK inhibitor (40μmmol/L of U0126). Also, SB203580 significantly inhibited TNF-α-induced monocyte adhesion in HUVEC. Superoxide production was minimal in the basal condition, however, treatment of TNF-α induced superoxide production in the dihydroethidine- loaded endothelial cells. Diphenyleneiodonium (DPI, 10μmol/L), an inhibitor of NADPH oxidase, and rotenone (1μmol/L), an inhibitor of mitochondrial complex I inhibited TNF-α-induced superoxide production, VCAM-1 expression and monocyte adhesion in the endothelial cells. Taken together, our data suggest that NADPH oxidase and mitochondrial ROS were involved in TNF-α-induced VCAM-1 and monocyte adhesion in the endothelial cells.

Keywords: Reactive oxygen species, p38 MAPK, Endothelial cells, Vascular cell adhesion molecule-1, Tumor necrosis factor-α