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Calcium-independent phospholipase Aβ-Akt signaling is involved in lipopolysaccharide-induced NADPH oxidase 1 expression and foam cell formation

Journal of Immunology, ISSN: 0022-1767, Vol: 183, Issue: 11, Page: 7497-7504
2009
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Article Description

Foam cell formation is the most important process in atherosclerosis, and low density lipoprotein oxidation by reactive oxygen species (ROS) is the key step in the conversion of macrophages to foam cells. This study reveals the control mechanism of the gene for NADPH oxidase 1 (Nox1), which produces ROS in the formation of foam cells by stimulating TLR4. Treatment of macrophages by the TLR4 agonist LPS stimulated ROS production and ROS-mediated macrophage to foam cell conversion. This LPS-induced ROS production and foam cell formation could be abrogated by pretreatment of macrophages with N-acetyl cysteine or apocynin. LPS increased Nox1 promoter activity, and resultant expression of mRNA and protein. Small interfering RNA mediated inhibition of Nox1 expression decreased LPS-induced ROS production and foam cell formation. LPS-mediated Nox1 expression and the responses occurred in a calcium-independent phospholipase A (iPLA)-dependent manner. The iPLAβ-specific inhibitor S-BEL or iPLAβ small interfering RNA attenuated LPS-induced Nox1 expression, ROS production, and foam cell formation. In addition, activation of iPLAβ by LPS caused Akt phosphorylation and was followed by increased Nox1 expression. These results suggest that the binding of LPS and TLR4 increases Nox1 expression through the iPLA β-Akt signaling pathway, and control ROS production and foam cell formation. Copyright © 2009 by The American Association of Immunologists, Inc.

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