Docosahexaenoic acid decreases TNF-α-induced lectin-like oxidized low-density lipoprotein receptor-1 expression in THP-1 cells.

Abstract

Docosahexaenoic acid (DHA) prevents atherosclerosis and may decrease monocyte/macrophage activation by tumor necrosis factor (TNF)-α. Here, we sought to determine the protective effects of DHA against TNF-α-induced stimulation of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) expression, which is associated with atherosclerosis. Using reverse transcription polymerase chain reaction, we found that TNF-α induced the expression of LOX-1 (OLR1), NADPH oxidase 2 (Nox2), p47phox (NCF1), very late antigen-4 (ITGA4), and lymphocyte function-associated antigen (ITGAL) genes. Additionally, DHA attenuated TNF-α-induced acetylated (Ac)-LDL uptake and reactive oxygen species (ROS) production, as measured using fluorescently labeled LDL and H2DCFDA, respectively, and reduced the expression levels of these genes. Moreover, the PI3 kinase inhibitor LY294002 blocked these effects of DHA. These results indicated that DHA inhibited several events associated with redox regulation in a PI3K-dependent manner, thereby mediating the expression of LOX-1 in monocytes/macrophages.

• Authors: Kazuo Yamagata, Chiaki Tusruta, Akane Ohtuski, Motoki Tagami
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 90 Issue 4 Pg. 125-32 (Apr 2014) ISSN: 1532-2823 [Electronic] Scotland
• PMID: 24518001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Chromones
• Integrin alpha Chains
• Lipoproteins, LDL
• Membrane Glycoproteins
• Morpholines
• OLR1 protein, human
• Onium Compounds
• Phosphoinositide-3 Kinase Inhibitors
• Reactive Oxygen Species
• Scavenger Receptors, Class E
• Tumor Necrosis Factor-alpha
• acetyl-LDL
• Docosahexaenoic Acids
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• diphenyleneiodonium
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Cell Line, Tumor
• Chromones (pharmacology)
• Docosahexaenoic Acids (pharmacology)
• Gene Expression
• Humans
• Integrin alpha Chains (genetics, metabolism)
• Lipoproteins, LDL (metabolism)
• Membrane Glycoproteins (antagonists & inhibitors, genetics, metabolism)
• Morpholines (pharmacology)
• NADPH Oxidase 2
• NADPH Oxidases (antagonists & inhibitors, genetics, metabolism)
• Onium Compounds (pharmacology)
• Oxidation-Reduction
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Reactive Oxygen Species (metabolism)
• Scavenger Receptors, Class E (genetics, metabolism)
• Transcriptional Activation (drug effects)
• Tumor Necrosis Factor-alpha (physiology)