Nitrated fatty acids prevent TNFalpha-stimulated inflammatory and atherogenic responses in endothelial cells.
Nitration products (nitroalkenes) of linoleic acid (LNO(2)) and oleic acid (OA-NO(2)) can act as endogenous PPARgamma ligands with electrophilic properties to exert anti-inflammatory effects on atherosclerotic plaques in the vasculature. Here, we show that OA-NO(2) and LNO(2) prevent tumor necrosis factor alpha (TNFalpha)-stimulated inflammatory and atherogenic responses in human umbilical vein endothelial cells (HUVECs). Both OA-NO(2) and LNO(2) prevented TNFalpha-stimulated release of the cytokines, IL-6, IL-8, IL-12/p40, IFNgamma, MCP-1, and IP-10, and inhibited NF-kappaB activation. OA-NO(2) and LNO(2) also blocked TNFalpha-induced expression of the adhesion molecules, ICAM-1, VCAM-1, and E-selectin, and suppressed monocyte adhesion to HUVECs. In each case, OA-NO(2) was more potent and efficacious than was LNO(2), possibly due to increased stability in aqueous media. Collectively, these results substantiate a new functional role for nitrated fatty acids, demonstrating that OA-NO(2) and LNO(2) exert an anti-inflammatory function against the inflammatory cascade initiated by the representative pro-inflammatory cytokine, TNFalpha.
Hwang
Jinah
J
Department of Food & Nutrition, Myongji University, Yongin, Republic of Korea.
Lee
Kang Eun
KE
Lim
Joong-Yeon
JY
Park
Sang Ick
SI
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D050197:Atherosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008041:Linoleic Acids / Q000494:pharmacology*; D009566:Nitrates / Q000494:pharmacology*; D009574:Nitro Compounds / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C501856:12-nitro-9,12-octadecadienoic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008041:Linoleic Acids; D009566:Nitrates; D009574:Nitro Compounds; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid