Diets rich in marine fish oil may protect against cardiovascular disease. Although the mechanisms involved in such protection are not known, fish oils have been reported to exert anti-inflammatory actions. For example, dietary fish oil supplementation was observed to profoundly decrease the numbers of monocytic cells adherent to endothelium overlying atherosclerotic lesions in pigs. We have therefore investigated the possibility that fish oil components-particularly n-3 polyunsaturated fatty acids (PUFAs)-might inhibit phagocyte-endothelium interactions. We have found that binding of a monocytic cell line (U937) to cultured endothelium (with cell adhesion molecules up- regulated by exposure to lipopolysaccharide [LPS], interleukin-1α, tumor necrosis factor-α, or phorbol myristate acetate [PMA)) is greatly decreased by pre-exposure of endothelial cells to n-3 and other PUFAs that are incidentally or purposefully oxidized; unoxidized PUFAs are completely ineffective. Decreased monocyte adherence probably derives from diminished up-regulation of endothelial cell adherence molecules VCAM-1 and ELAM-1. Oxidized n-3 PUFAs prevent LPS- or PMA-induced activation of transcription factor NF-κB and the consequent induction of mRNA for both cell adhesion molecules. Hydroperoxy fatty acids are the active principle in oxidized PUFAs because the activity (1) is predominantly organic soluble, (2) is obliterated by pretreatment of oxidized material with chemical reducing agents, and (3) is diminished by enzymatic reduction of organic hydroperoxides with glutathione/glutathione peroxidase. We speculate that this suppression of phagocyte-endothelium interactions by oxidized PUFAs may help explain the anti-inflammatory and possible anti-atherogenic effects of diets rich in fish oil. Perhaps more importantly, this modulation of endothelial cell adhesion molecule expression by oxidized lipids may represent a natural mechanism whereby inflammation-mediated oxidation of endothelial PUFAs may retard ingress of phagocytes and thereby prevent unrestrained phlogistic responses.
ASJC Scopus subject areas
- Pathology and Forensic Medicine