NDLI: Calcium-independent phospholipase A2beta-Akt signaling is involved in lipopolysaccharide-induced NADPH oxidase 1 expression and foam cell formation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hong, Seong Yeon Kim, Jae-Ryong Lee, Chu-Hee Baek, Suk-Hwan Lee, Sun-Hye Park, Dae-Weon Park, Sung Chul Park, Yun-Ki
Description	Country affiliation: South Korea Author Affiliation: Lee SH ( Aging-associated Vascular Disease Research Center, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, South Korea.)
Abstract	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(2) (iPLA(2))-dependent manner. The iPLA(2)beta-specific inhibitor S-BEL or iPLA(2)beta small interfering RNA attenuated LPS-induced Nox1 expression, ROS production, and foam cell formation. In addition, activation of iPLA(2)beta 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(2)beta-Akt signaling pathway, and control ROS production and foam cell formation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Foam Cells Immunology Gene Expression Regulation Group Iv Phospholipases A2 Nadh, Nadph Oxidoreductases Proto-oncogene Proteins C-akt Signal Transduction Animals Atherosclerosis Metabolism Blotting, Western Calcium Signaling Cell Line Flow Cytometry Gene Expression Lipopolysaccharides Mice Microscopy, Confocal Rna, Small Interfering Reactive Oxygen Species Reverse Transcriptase Polymerase Chain Reaction Toll-like Receptor 4 Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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