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Cardiovascular Research 1997 34(3):529-535; doi:10.1016/S0008-6363(97)00060-6
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

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

Mayumi Okada, Akihiko Suzuki, Kimio Mizuno, Yoshimasa Asada, Yasushi Ino, Tomoyuki Kuwayama, Koji Tamakoshi, Shigehiko Mizutani* and Yutaka Tomoda

Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466, Japan

* Corresponding author. Tel.: +81 (52) 744-2261; fax: +81 (52) 744-2268.

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 17β-estradiol (E2, 10–9 ~10–6 M) inhibited the 10 µg/ml-induced migration of THP-1 cells in a dose-dependent manner, estrone (E1), estriol (E3) 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 E2. Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10–6 M), significantly antagonized the inhibitory effect of 10–7 M E2. m-ox-LDL stimulated MCP-1 secretion from THP-1 cells, which was reduced by E2. Anti-human MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by m-ox-LDL. E2 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 E2 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.

KEYWORDS Estrogen; Progestin; Monocytes; Minimally oxidized LDL; Migration; MCP-1; Postmenopausal hormone replacement therapy; Atherosclerosis


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