NADPH Oxidase and Mitochondrial ROS are Involved in the TNF-alpha-induced Vascular Cell Adhesion Molecule-1 and Monocyte Adhesion in Cultured Endothelial Cells.
- Author:
Jae Hyeon YU
1
;
Cuk Seong KIM
;
Dae Goon YOO
;
Yun Jeong SONG
;
Hee Kyoung JOO
;
Gun KANG
;
Ji Yoon JO
;
Jin Bong PARK
;
Byeong Hwa JEON
Author Information
1. Department of Thoracic Surgery, College of Medicine, Chungnam National University, Daejeon, Korea.
- Publication Type:Original Article
- Keywords:
Reactive oxygen species;
p38 MAPK;
Endothelial cells;
Vascular cell adhesion molecule-1;
Tumor necrosis factor-alpha
- MeSH:
Atherosclerosis;
Endothelial Cells*;
Monocytes*;
NADP*;
NADPH Oxidase*;
p38 Mitogen-Activated Protein Kinases;
Reactive Oxygen Species;
Rotenone;
Superoxides;
Tumor Necrosis Factor-alpha;
U937 Cells;
Vascular Cell Adhesion Molecule-1*
- From:The Korean Journal of Physiology and Pharmacology
2006;10(4):217-222
- CountryRepublic of Korea
- Language:English
-
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-alpha 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-alpha (15 ng/ml). Ten micromol/L of SB203580, an inhibitor of p38 MAPK, significantly reduced TNF-alpha-induced VCAM-1 expression, compared to the JNK inhibitor (40micromol/L of SP60015) or ERK inhibitor (40micrommol/L of U0126). Also, SB203580 significantly inhibited TNF-alpha-induced monocyte adhesion in HUVEC. Superoxide production was minimal in the basal condition, however, treatment of TNF-alpha induced superoxide production in the dihydroethidine-loaded endothelial cells. Diphenyleneiodonium (DPI, 10micromol/L), an inhibitor of NADPH oxidase, and rotenone (1micromol/L), an inhibitor of mitochondrial complex I inhibited TNF-alpha-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-alpha-induced VCAM-1 and monocyte adhesion in the endothelial cells.
