The estrogen metabolite 17β-dihydroequilenin counteracts interleukin-1α induced expression of inflammatory mediators in human endothelial cells in vitro via NF-κB pathway

Svitlana Demyanets; Stefan Pfaffenberger; Christoph Kaun; Gersina Rega; Walter S. Speidl; Stefan P. Kastl; Thomas W. Weiss; Philipp J. Hohensinner; Wolf Dietrich; Walter Tschugguel; Valery N. Bochkov; Ezzat M. Awad; Gerald Maurer; Kurt Huber; Johann Wojta

doi:10.1160/TH05-05-0333

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(01): 107-116
DOI: 10.1160/TH05-05-0333

Endothelium and Vascular Development

Schattauer GmbH

The estrogen metabolite 17β-dihydroequilenin counteracts interleukin-1α induced expression of inflammatory mediators in human endothelial cells in vitro via NF-κB pathway

Svitlana Demyanets^*

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

³Department of Therapy and Clinical Pharmacology, Kharkov Medical University, Ukraine

,

Stefan Pfaffenberger^*

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Christoph Kaun

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Gersina Rega

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Walter S. Speidl

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Stefan P. Kastl

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Thomas W. Weiss

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Philipp J. Hohensinner

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Wolf Dietrich

⁴Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University Vienna

,

Walter Tschugguel

⁴Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University Vienna

,

Valery N. Bochkov

⁵Department of Vascular Biology and Thrombosis Research, Medical University Vienna, Austria

,

Ezzat M. Awad

⁵Department of Vascular Biology and Thrombosis Research, Medical University Vienna, Austria

,

Gerald Maurer

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

,

Kurt Huber

²3^rd Medical Department for Cardiology and Emergency Medicine, Wilhelminenspital, Vienna, Austria

,

Johann Wojta

¹Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria

› Author Affiliations

Abstract

Summary

In most studies showing cardio- and vasculoprotective effects of estrogens, 17β-estradiol was used and little information on possible effects of different estrogen metabolites is yet available. We investigated whether particular estrogen metabolites are effective in counteracting inflammatory activation of human endothelium. Human endothelial cells were incubated with 17α-dihydroequilenin, 17β-dihydroequilenin, δ-8,9-dehydroestrone, estrone and 17β-estradiol and stimulated with interleukin (IL)-1α.The expression of IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) was determined. 17β-dihydroequilenin and 17β-estradiol at a concentration of 1µM reduced IL-1α-induced up regulation of IL-6, IL-8 and MCP-1 close to control levels. When both compounds were used in combination an additive effect was observed. 17α-dihydroequilenin and δ-8,9-dehydroestrone showed a similar anti-inflammatory effect only when used at 10µM whereas estrone had no effect. The effect of 17β-dihydroequilenin on IL-1α-induced production of IL-6, IL-8 and MCP-1 was reversed by the estrogen receptor antagonist ICI 182,780. 17β-dihydroequilenin also inhibited IL-1α-induced translocation of p50 and p65 to the nucleus of the cells. We have identified the estrogen metabolite 17β-dihydroequilenin, as an inhibitor of inflammatory activation of human endothelial cells. Characterization of specific estrogens – as shown in our study – could provide the basis for tailored therapies, which might be able to achieve vasoprotection without adverse side effects.

Keywords

Estrogens - endothelial cells - cardiovascular effects - inflammation - cytokines

Full Text

References

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