Estradiol reduces basal and cytokine induced monocyte adhesion to endothelial cells

Objective: To investigate the effect of 17β-estradiol (E 2) on binding of monocytes to human aortic endothelial cells (HAECs) with or without cytokine induction. Methods: Confluent monolayers of HAECs were incubated with or without E 2 for 48 h prior to the monocyte adhesion assay. In studies with cytokines, 1 ng/ml tumor necrosis factor-α (TNF-α), 20 U/ml interleukin-1β (IL-1β) or both were added to the culture medium for the final 24 or 4 h. For the measurement of monocyte adhesion, 3H-thymidine labeled human THP-1 monocytes (4×10 5 cells per well) were added to the confluent monolayer of HAECs and incubated at 37 °C for 90 min. The unbound THP-1 cells were removed by gentle washing, and bound cells were digested with NaOH and quantified by measuring radioactivity. Results: When HAECs were pretreated for 48 h with E 2 the basal adhesion of THP-1 cells was reduced by an average of 28%. Estrogen significantly reduced cytokine-induced adhesion by 30–35% when the cytokines were added for 4 h. When the cytokine treatment was prolonged to 24 h, pretreatment of HAECs with E 2 had no effect on THP-1 cell adhesion. Conclusions: E 2 reduces basal and short-term cytokine induced monocyte binding to HAECs. Since monocyte adhesion to vascular endothelial cells is one of the initial steps in the pathogenesis of atherosclerosis, E 2 may mediate vascular protection by reducing monocyte-endothelial cell binding in the early stages of atherogenesis.