Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions

Abstract

The antiatherogenic effects of soy isoflavone consumption have been demonstrated in a variety of studies. However, the mechanisms involved remain poorly defined. Adhesion of monocytes to vascular endothelial cells is a key step within the inflammatory cascade that leads to atherogenesis. Many factors, including the physical forces associated with blood flow, regulate this process. Using an in vitro flow assay, we report that genistein, a principal component of most isoflavone preparations, inhibits monocyte adhesion to cytokine (TNF-alpha)-stimulated human vascular endothelial cells at physiologically relevant concentrations (0-1 microM). This effect is absolutely dependent on flow and is not observed under static conditions. Furthermore, this inhibition was dependent on activation of endothelial peroxisomal proliferator-activated receptor-gamma. No significant role for other reported properties of genistein, including antioxidant effects, inhibition of tyrosine kinases, or activation of estrogen receptors, was observed. Furthermore, the antiadhesive effects of genistein did not occur via modulation of the adhesion molecules E-selectin, ICAM-1, VCAM-1, or platelet-endothelial cell adhesion molecule-1. These data reveal a novel anti-inflammatory mechanism for isoflavones and identify the physical forces associated with blood flow and a critical mediator of this function.

Endothelial Surface N-Glycans Mediate Monocyte Adhesion and Are Targets for Anti-inflammatory Effects of Peroxisome Proliferator-activated Receptor γ Ligands

“…Primary human monocytes were isolated using histopaque density gradients from healthy volunteers according to Institutional IRB approved protocols as previously described (20). Cell Tracker Green (CMFDA, C2925) fluorescent dye was purchased from Molecular Probes Inc., Eugene, OR.…”

“…Cell Culture and Viability-HUVEC and HAEC were cultured as previously described (20) and used between passages 3 and 7. All experiments were performed within 1 day of cells reaching confluence.…”

“…Our recent studies suggest that PPAR␥ ligand treatment of endothelial cells under static conditions attenuates subsequent TNF␣-dependent monocyte rolling and adhesion. Moreover, this effect is independent of TNF␣-dependent increased adhesion molecule expression (19,20). However, the mechanism for this effect remains unclear.…”

The Effect of Soy Protein Beverages on Serum Cell Adhesion Molecule Concentrations in Prehypertensive/Stage 1 Hypertensive Individuals

“…The isoflavones, genistein, daidzein, and glycitein (and their respective glycosides), found in soy foods have anti-inflammatory properties (Chacko et al 2005;Wei et al 1995), but this has not been confirmed in uncomplicated HTN (prehypertension/Stage I HTN). Genistein has been shown to have a potent anti-inflammatory action via inhibiting monocyte adhesion to cytokine-activated endothelial cells (Chako et al 2005).…”

“…The isoflavones found in soy foods, genistein, daidzein, and glycitein (and their respective glycosides), have been reported to have anti-inflammatory properties (Chacko et al 2005;Wei et al 1995). Atteritano et al (2007) supplemented postmenopausal women with 54 mg/day of genistein for 2 years and found sVCAM-1 and sICAM-1 to be significantly (P < 0.05) reduced compared to placebo.…”