title: Linoleic acid increases monocyte chemotaxis and adhesion to human aortic endothelial cells through protein kinase C- and cyclooxygenase-2-dependent mechanisms.
abstract: The effects of polyunsaturated n-6 linoleic acid on monocyte-endothelial interactions were investigated with particular emphasis on the expression of platelet/endothelial cell adhesion molecule (PECAM)-1 and the role of protein kinase C (PKC) and cyclooxygenase-2 (COX-2). As a diet rich in polyunsaturated fatty acids may favour atherosclerosis in hyperglycaemia, this study was performed in both normal and high-glucose media using human aortic endothelial cells (HAEC). The HAEC were preincubated with normal (5 mM) or high (25 mM) D-glucose for 3 days before addition of fatty acids (0.2 mM) for 3 days. Linoleic acid enhanced PECAM-1 expression independently of tumor necrosis factor (TNF)-α and significantly increased TNF-α-induced monocyte adhesion to HAEC in comparison to the monounsaturated n-9 oleic acid. Chronic glucose treatment (25 mM, 6 days) did not modify the TNF-α-induced or fatty acid-induced changes in monocyte binding. The increase in monocyte binding was accompanied by a significant increase in E-selectin and vascular cell adhesion molecule (VCAM)-1 expression and could be abrogated by an interleukin (IL)-8 neutralising antibody and by the PKC and COX inhibitors. Inhibition of PKC-δ reduced VCAM-1 expression regardless of experimental condition and was accompanied by a significant decrease in monocyte binding. Conditioned medium from linoleic acid-treated HAEC grown in normal glucose conditions significantly increased THP-1 chemotaxis. These results suggest that linoleic acid-induced changes in monocyte chemotaxis and subsequent binding are not solely mediated by changes in adhesion molecule expression but may be due to secreted factors such as IL-8, monocyte chemoattractant protein-1 or prostaglandins (PGs) such as PGE(2), as IL-8 neutralisation and COX-2 inhibition reduced monocyte binding without changes in adhesion molecule expression.
authors.affiliation: Centre for Public Health, School of Medicine, Dentistry & Biomedical Sciences, Queen's University, Belfast, UK.
authors.forename: Nuria
authors.initials: N
authors.lastname: Matesanz
authors.forename: Victoria
authors.initials: V
authors.lastname: Jewhurst
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Trimble
authors.forename: Ann
authors.initials: A
authors.lastname: McGinty
authors.forename: Daphne
authors.initials: D
authors.lastname: Owens
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Tomkin
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Powell
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019040:E-Selectin; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D019787:Linoleic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011493:Protein Kinase C