Caffeic Acid Disturbs Monocyte Adhesion onto Cultured Endothelial Cells Stimulated by Adipokine Resistin

Adipokines have been implicated in the pathogenesis of atherosclerosis via pro-inflammatory mechanisms contributing to insulin resistance. The adipokine resistin causes endothelium dysfunction, which plays an important role in sustaining atherogenesis. This study investigated whether resistin induced expression of cell adhesion molecules and integrins in endothelial cells and THP-1 monocytes and whether such induction was attenuated by 1-20 mu M caffeic acid. Resistin enhanced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1), and E-selectin and monocyte expression of beta 1, beta 2, and alpha 4 integrins. The enhancement of these proteins was diminished by caffeic acid with reduced THP-1 cell adhesion on activated endothelium. Caffeic acid at <= 20 mu M demoted resistin-stimulated interleukin 8 (IL-8) production responsible for ICAM-1 and beta 2 integrin induction. The endothelial up-regulation of IL-8 secretion by resistin entailed toll-like receptor 4 (TLR4) activation, but caffeic acid diminished IL-8 production and TLR4 induction. Furthermore, caffeic acid encumbered resistin-activated nuclear factor kappa B (NF-kappa B) signaling. These results demonstrate that caffeic acid blocked monocyte trafficking to resistin-activated endothelium via disturbing NF-kappa B signaling responsive to IL-8. Therefore, caffeic acid may have therapeutic potential in preventing obesity-associated atherosclerosis.