Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP-1 cells stimulated by minimally oxidized low-density lipoprotein in vitro

Objective: Many epidemiological studies have shown that postmenopausal hormone replacement therapy (HRT) has a beneficial effect on atherosclerotic cardiovascular disease. The aim of this study was to investigate the effects of estrogen and progestin on the migration of monocytes induced by minimally oxidized low-density lipoprotein (m-ox-LDL) in vitro. Methods: Human monocytic THP-1 cells were used for the study. Migration assay was performed using a modified Boyden chamber. Results: The presence of estrogen receptors was determined in THP-1 cells by Western and Northern blot analysis. Although native LDL had no significant effects on the migration of THP-1 cells, m-ox-LDL increased the migration of THP-1 cells in a dose-dependent manner. Although 17 beta-estradiol (E-2, 10(-9) - 10(-6) M) inhibited the 10 mu g/ml-induced migration of THP-1 cells in a dose-dependent manner, estrone (E-1), estriol (E-3) and progesterone (P) had no significant effects. The combination of P (10(-9) - 10(-6) M) did not show any effect on the inhibitory effect of 10(-7) M E-2. Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10(-6) M), significantly antagonized the inhibitory effect of 10(-7) M E-2. m-ox-LDL stimulated MCP-1 secretion from THP-1 cells, which was reduced by E-2. Anti-human MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by m-ox-LDL. E-2 also inhibited the 10 ng/ml MCP-1-induced migration of THP-1 cells in a dose-dependent manner. Conclusions: These findings suggest that the inhibitory effect of E-2 on the migration of monocytes might be one of the factors involved in the decreased incidence of atherosclerotic cardiovascular disease in premenopausal women and postmenopausal HRT.