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

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• 作者：Nuria Matesanz^a ; Victoria Jewhurst^a ; Elisabeth R. Trimble^a ; Ann McGinty^a ; Daphne Owens^b ; Gerald H. Tomkin^b ; Lesley A. Powell^a ; ^{l.powell@qub.ac.uk}
• 关键词：Endothelial cells ; Fatty acids ; Adhesion molecules ; Monocyte adhesion ; Monocyte chemotaxis ; Inflammation
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2012
• 期刊代码：70_09552863
• 类别：abs
• 出版时间：June, 2012
• 卷：23
• 期：6
• 页码：685-690
• 文件大小：287 K

摘要

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)-伪 and significantly increased TNF-伪-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-伪-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-未 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.