Abstract
Background: ω-3 fatty acids have beneficial effects in chronic inflammatory diseases that are characterized by accumulation of leukocytes and leukocyte-mediated tissue injury. Accumulation of leukocytes occurs, in part, due to pro-inflammatory responses in endothelial cells, such as increase in expression of leukocyte adhesion receptors and chemokines, such as MCP-1 and IL-8. Methods: ω-3 fatty acids, such as EPA, are highly polyunsaturated and readily undergo auto-oxidation. We studied the effect of oxidized EPA and unoxidized (native) EPA on leukocyte-glomerular endothelial cell interactions using adhesion assays, ELISA assays and transmigration assays. We used electrophoresis mobility shift assays to determine the effect of oxidized and unoxidized EPA on cytokine-induced nuclear factor-κB (NF-κB) activation. Results: Oxidized EPA but not unoxidized EPA dose-dependently inhibits cytokine-induced leukocyte adhesion receptors on glomerular endothelial cells, which correlates with inhibition of leukocyte-glomerular endothelial cell interactions. Oxidized EPA but not unoxidized EPA inhibits cytokine-induced glomerular endothelial and mesangial cell expression of MCP-1, and to a lesser extent IL-8. Transmigration assays show that oxidized EPA but not unoxidized EPA inhibits leukocyte transmigration across glomerular endothelial cells. Oxidized EPA but not unoxidized EPA potently inhibited cytokine-induced activation of NF-κB in glomerular endothelial and mesangial cells. Conclusions: These studies show that the beneficial effects of fish oil in chronic inflammatory diseases, including IgA nephropathy, may result from the inhibitory effects of oxidized ω-3 fatty acids on pro-inflammatory events in endothelial cells via inhibition of NF-κB activation.
Original language | English (US) |
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Pages (from-to) | e136-e145 |
Journal | Nephron - Experimental Nephrology |
Volume | 97 |
Issue number | 4 |
DOIs | |
State | Published - 2004 |
Keywords
- Endothelial interactions
- Leukocytes
- MCP-1
- NF-κB
- Oxidized EPA
ASJC Scopus subject areas
- Physiology
- Genetics
- Nephrology