title: Docosahexaenoic acid inhibits inflammation via free fatty acid receptor FFA4, disruption of TAB2 interaction with TAK1/TAB1 and downregulation of ERK-dependent Egr-1 expression in EA.hy926 cells.
abstract: METHODS
  Inflammation is intimately associated with many cardiovascular events and docosahexaenoic acid (DHA) has been shown to protect against CVD. Egr-1 has emerged as a key regulator in the development of atherosclerosis. Free fatty acid receptor 4 (FFA4) is an n-3 FA membrane receptor. Tumor necrosis factor alpha (TNF-α) is an inflammatory mediator and transforming growth factor-β-activated kinase 1 (TAK1) is essential in the TNF-α-mediated activation of NF-κB. We examined the mechanisms underlying DHA inhibition of inflammation in human EA.hy926 cells.
  
  
  RESULTS
  TNF-α markedly induced the interaction between TAK1 binding protein (TAB) 2 and TAK1/TAB1, the phosphorylation of ERK, p38 MAPK and Akt, the expression of Egr-1 and ICAM-1, and HL-60 (monocyte-like) cell adhesion. Pretreatment with DHA attenuated TNF-α-induced phosphorylation of ERK, expression of Egr-1 and ICAM-1 and HL-60 cell adhesion. Transfection with siFFA4 reversed the DHA-mediated inhibition of TNF-α-induced Egr-1 and ICAM-1 expression, HL-60 cell adhesion and NF-κB and DNA-binding activity.
  
  
  CONCLUSIONS
  Our results suggest that the anti-inflammatory effect of DHA on the endothelium is at least partially linked to FFA4, disruption of TAB2 interaction with TAK1/TAB1 and downregulation of ERK-dependent Egr-1 and ICAM-1 expression, which leads to less HL-60 cell adhesion to TNF-α-stimulated EA.hy926 cells.
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung, Taiwan.|Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liu
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Ting-Wen
authors.initials: TW
authors.lastname: Chia
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Lu
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung, Taiwan.|Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chien-Chun
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.|Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Haw-Wen
authors.initials: HW
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004281:Docosahexaenoic Acids; D051766:Early Growth Response Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases; D018799:Intercellular Adhesion Molecule-1; D020930:MAP Kinase Kinase Kinases; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C497325:EGR1 protein, human; C519853:FFAR4 protein, human; C486300:TAB1 protein, human; C410585:TAB2 protein, human
keywords: Docosahexaenoic acid (DHA); Early growth response protein 1 (Egr-1); Free fatty acid receptor 4 (FFA4); Inflammation; Tumor necrosis factor alpha (TNF-α)