Docosahexaenoic acid inhibits cytokine-induced expression of P-selectin and neutrophil adhesion to endothelial cells

Dietary polyunsaturated fatty acids, such as docosahexaenoic acid, may inhibit pathological processes involving endothelial cell activation. Herein, it was found that treatment of endothelial cells with docosahexaenoic acid dose dependently reduced neutrophil adhesion provoked by tumor necrosis factor-alpha (TNF-alpha). In fact, pretreatment with 100 muM of docosahexaenoic acid for 24 In decreased TNF-alpha-induced neutrophil adhesion by 50%, Moreover, this pretreatment with docosahexaenoic acid (100 muM, 24 h) down-regulated TNF-alpha-induced endothelial cell surface expression of P-selection by 75%. Importantly, immunoneutralization of P-selectin reduced neutrophil adhesion to TNF-alpha-activated endothelial cells by more than 50%, indicating a significant role of P-selectin in this model. On the other hand, CXC chemokines, i.e. macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC), are also important regulators of neutrophil activation and adhesion. However, pretreatment with docosahexaenoic acid had no effect on TNF-alpha-provoked production of MIP-2 and KC in endothelial cells. Our study provide evidence that docosahexaenoic acid inhibits expression of P-selectin and subsequent adhesion of neutrophils to endothelial cells in response TNF-alpha, which may help explain the anti-inflammatory effects exerted by docosahexaenoic acid, (C) 2002 Elsevier Science B.V. All rights reserved.