13‐HPODE and 13‐HODE modulate cytokine‐induced expression of endothelial cell adhesion molecules differently

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 microM. Higher concentrations were toxic. Similar effects were observed with H2O2 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 microM 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.

Excessive dietary linoleic acid induces proinflammatory markers in rats

“…Also, we demonstrated that exposure of rat endothelial cells to ARA did not alter the expression of the adhesion molecules VCAM-1 and ICAM-1 (data not shown). Several studies also reported that OXLAMs could promote inflammation by modulating proinflammatory cytokines IL-1β and TNF-α levels through the NF-κB pathway [25,71,75,76]. In humans, Ramsden et al [36] showed that lowering dietary LA reduces plasma OXLAMs levels reinforcing the direct link between LA and its circulating oxidized metabolites.…”

Selenium in Biology: Facts and Medical Perspectives

“…In atherosclerotic lesions, hydroperoxides as well as the 15-lipoxygenase were found (Ylä-Herttuala, 1991), and lipid hydroperoxides can induce adhesion molecules in cultivated endothelium cells (Friedrichs et al, 1999). Both oxLDL-induced foam cell formation and smooth muscle cell proliferation and hydroperoxide-induced presentation of adhesion molecules are considered to synergize in the initiation of atherogenesis.…”

Phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to intracellular adhesion molecule-1

“…In addition, lipid hydroperoxidederived short-chain aldehydes, such as 4-hydroxy-2-nonenal (HNE), are reported to modulate proatherogenic responses (22). Lysophosphatidylcholine (LysoPC) and hydro(pero)xy fatty acids, such as hydro(pero)xyoctadecadienoic acid [H(p)ODE] and hydro(pero)xyeicosatetraenoic acid [H(p)ETE], have been reported to induce expression of cell adhesion molecules in endothelial cells (23)(24)(25). LysoPC and hydro(pero)xy fatty acids might be generated in atherosclerotic lesions by certain phospholipase A 2 (PLA 2 ) enzymes (26,27).…”