Linoleic acid increases monocyte chemotaxis and adhesion to human aortic endothelial cells through protein kinase C- and cyclooxygenase-2-dependent mechanisms

• Published in: The Journal of nutritional biochemistry 2012-06, Vol.23 (6), p.685-690
• Main Authors: Matesanz, Nuria, Jewhurst, Victoria, Trimble, Elisabeth R, McGinty, Ann, Owens, Daphne, Tomkin, Gerald H, Powell, Lesley A
• Format: Article
• Language: English
• Subjects: adhesion; Adhesion molecules; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; atherosclerosis; Biological and medical sciences; Blood Glucose - analysis; cell adhesion; Cell Adhesion Molecules - drug effects; Cells, Cultured; chemoattractants; Chemokine CCL2 - metabolism; chemotaxis; Chemotaxis, Leukocyte - drug effects; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; diet; E-Selectin - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fatty acids; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; glucose; Humans; Inflammation; interleukin-8; Interleukin-8 - metabolism; linoleic acid; Linoleic Acid - pharmacology; Monocyte adhesion; Monocyte chemotaxis; Monocytes - drug effects; neutralization; neutralizing antibodies; oleic acid; Platelet Endothelial Cell Adhesion Molecule-1 - genetics; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; polyunsaturated fatty acids; prostaglandins; protein kinase C; Protein Kinase C - metabolism; Tumor Necrosis Factor-alpha - metabolism; tumor necrosis factors; Vascular Cell Adhesion Molecule-1 - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2011.03.020

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 PGE2, as IL-8 neutralisation and COX-2 inhibition reduced monocyte binding without changes in adhesion molecule expression.