Affiliations: German Institute of Human Nutrition, Potsdam‐Rehbrücke, Germany | Departments of Surgery and Nutrition and Food Science, University of Kentucky, USA | Institute of Nutritional Science, University of Potsdam, Germany
Note: [] Corresponding author: Prof. Dr Regina Brigelius‐Flohé, German Institute of Human Nutrition, Arthur‐Scheunert‐Allee 114‐116, D‐14558 Bergholz‐Rehbrücke, Germany. Tel.: (49)033200/88353; Fax: (49)033200/88407; E‐mail: Flohe@ www.dife.de.
Abstract: Expression of cellular adhesion molecules (CAMs) at endothelial surfaces represents a physiological response to vascular damage and mediates the initiation of inflammation and possibly of atherogenesis. The cytokines TNF\alpha and IL‐1 are potent inducers of CAMs in endothelial cells. Reactive oxygen species comprising lipid oxidation products have been implicated in the signaling pathways of both TNF\alpha and IL‐1 and accordingly could modulate atherogenic events. We, therefore, investigated the potential role of the lipoxygenase product, 13‐hydroperoxyoctadecadienoic acid (13‐HPODE), which has also been identified in oxidized low density lipoproteins on CAM expression in HUVEC. 13‐HPODE induced the expression of ICAM‐1 in a concentration dependent manner up to 75 \muM. Higher concentrations were toxic. Similar effects were observed with H_{2}O_{2} and phosphatidylcholine hydroperoxide. VCAM‐1 and E‐selectin were not induced by 13‐HPODE. 13‐HPODE administered simultaneously with IL‐1 or TNF\alpha induced ICAM‐1 additively, suggesting that hydroperoxides and cytokines act on the same signaling pathways. In contrast, pretreatment of cells with 50 \muM 13‐HPODE for 1 hour rather inhibited subsequent cytokine‐induced ICAM‐1 and E‐selectin expression. Surprisingly, the reduction product of 13‐HPODE, 13‐hydroxyoctadecadienoic acid (13‐HODE) proved to be an even better inducer of ICAM‐1 than 13‐HPODE. Pretreatment with 13‐HODE did not show any inhibitory effect on ICAM‐1 expression. Our data show that lipoxygenase products differentially affect CAM expression. 13‐HPODE is stimulatory by itself and can positively or negatively affect cytokine signaling depending on time of exposure. 13‐HODE induces CAM expression by itself but does not inhibit cytokine signaling. Thus, the interplay of lipoxygenase products with proinflammatory cytokines can not simply be explained by an oxidant‐mediated facilitation of cytokine signaling.
Journal: Biofactors, vol. 9, no. 1, pp. 61-72, 1999
