Korean J Physiol Pharmacol.  2006 Aug;10(4):217-222.

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

• Yu JH
• Kim CS
• Yoo DG
• Song YJ
• Joo HK
• Kang G
• Jo JY
• Park JB
• Jeon BH

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.

Keyword

Reactive oxygen species; p38 MAPK; Endothelial cells; Vascular cell adhesion molecule-1; Tumor necrosis factor-alpha

MeSH Terms

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*
NADP
NADPH Oxidase
Reactive Oxygen Species
Rotenone
Superoxides
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
p38 Mitogen-Activated Protein Kinases