Abstract
Increased intake of saturated fatty acids (SFAs), such as palmitate (Pal), is linked to a higher risk of type 2 diabetes and cardiovascular disease. Although recent studies have investigated the direct effects of SFAs on inflammatory responses in vascular endothelial cells, it remains unknown whether SFAs also induce these responses mediated by circulating cells. In this study, especially focused on adhesion molecules and monocytes, we investigated the indirect effects of Pal on expression and release of ICAM-1 and E-selectin in vascular endothelial cells. Phorbol 12-myristate 13-acetate (PMA)-treated THP-1 (pTHP-1) cells and human monocytes were stimulated with various free fatty acids (FFAs). SFAs, but not unsaturated fatty acids (UFAs), increased interleukin (IL)-1β secretion and decreased IL-1 receptor antagonist (IL-1Ra) secretion, resulting in an increase in the IL-1β/IL-1Ra secretion ratio. UFAs dose-dependently inhibited the increase in IL-1β secretion and decrease in IL-1Ra secretion induced by Pal. Moreover, in human aortic and vein endothelial cells, expression and release of ICAM-1 and E-selectin were induced by treatment with conditioned medium collected from Pal-stimulated pTHP-1 cells and human monocytes, but not by Pal itself. The up-regulated expression and release of adhesion molecules by the conditioned medium were mostly abolished by recombinant human IL-1Ra supplementation. These results suggest that the Pal-induced increase in the ratio of IL-1β/IL-1Ra secretion in monocytes up-regulates endothelial adhesion molecules, which could enhance leukocyte adhesion to endothelium. This study provides further evidence that IL-1β neutralization through receptor antagonism may be useful for preventing the onset and development of cardiovascular disease.