NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production.

Oxidation-reduction (redox) coupled mechanisms play an important role in the regulation of cell surface adhesion molecule expression. In endothelial cells membrane-bound NADH/NADPH oxidase is a significant source of intracellular superoxide (O(2)(-)) production. We explored the role of flavin containing proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene expression in human aortic endothelial cells (HAECs) and human dermal microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(-)production within 5 min as determined by lucigenin chemiluminescence analysis of whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation. However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF- alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter gene constructs in transiently transfected HMECs. These data suggest that flavin binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not necessary for NF- kappa B activation or for transactivation of NF- kappa B driven promoters.

Tummala PE ，Chen XL ，Medford RM 《JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY》

Rac1 and superoxide are required for the expression of cell adhesion molecules induced by tumor necrosis factor-alpha in endothelial cells.

Chen XL ，Zhang Q ，Zhao R ，Ding X ，Tummala PE ，Medford RM ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors: role of the nuclear transcription factor NF-kappa B.

Dhawan S ，Singh S ，Aggarwal BB 《EUROPEAN JOURNAL OF IMMUNOLOGY》

Regulation of adhesion molecule expression in human endothelial and smooth muscle cells by omega-3 fatty acids and conjugated linoleic acids: involvement of the transcription factor NF-kappaB?

Goua M ，Mulgrew S ，Frank J ，Rees D ，Sneddon AA ，Wahle KW ... -  《PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS》

4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-kappaB-DNA-binding activity.

Lee G ，Na HJ ，Namkoong S ，Jeong Kwon H ，Han S ，Ha KS ，Kwon YG ，Lee H ，Kim YM ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》