title: 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: Laboratory of Molecular Health Science of Food, Department of Food Bioscience and Biotechnology, College of Bioresourse Science, Nihon University (NUBS), Japan; Advance Research Center on Food Function, College of Bioresourse Science, Nihon University (NUBS), Japan. Electronic address: kyamagat@brs.nihon-u.ac.jp.
authors: Kazuo
authors: K
authors: Yamagata
authors: Laboratory of Molecular Health Science of Food, Department of Food Bioscience and Biotechnology, College of Bioresourse Science, Nihon University (NUBS), Japan.
authors: Chiaki
authors: C
authors: Tusruta
authors: Laboratory of Molecular Health Science of Food, Department of Food Bioscience and Biotechnology, College of Bioresourse Science, Nihon University (NUBS), Japan.
authors: Akane
authors: A
authors: Ohtuski
authors: Department of Internal Medicine, Sanraku Hospital, Chiyoda-Ku, Tokyo, Japan.
authors: Motoki
authors: M
authors: Tagami
mesh_terms: D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D002867:Chromones; D004281:Docosahexaenoic Acids; D039001:Integrin alpha Chains; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D009025:Morpholines; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009861:Onium Compounds; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; C495137:OLR1 protein, human; C032629:acetyl-LDL; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C007517:diphenyleneiodonium; C056558:CYBB protein, human; C060505:neutrophil cytosolic factor 1
keywords: Ac-LDL; DHA; LOX-1; ROS; TNF-α