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Estrogen and Progesterone Modulate Monocyte Cell Cycle Progression and Apoptosis

Authors

  • T. Thongngarm,

    1. Division of Rheumatology, G.V. (Sonny) Montgomery VAMC and Division of Rheumatology/Molecular Immunology, University of Mississippi Medical Center, Jackson, MS, USA and Division of Allergy and Immunology, Department of Medicine, University of Colorado Health Sciences Center, CO, USA
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  • J. K. Jenkins,

    1. Division of Rheumatology, G.V. (Sonny) Montgomery VAMC and Division of Rheumatology/Molecular Immunology, University of Mississippi Medical Center, Jackson, MS, USA and Division of Allergy and Immunology, Department of Medicine, University of Colorado Health Sciences Center, CO, USA
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  • K. Ndebele,

    1. Division of Rheumatology, G.V. (Sonny) Montgomery VAMC and Division of Rheumatology/Molecular Immunology, University of Mississippi Medical Center, Jackson, MS, USA and Division of Allergy and Immunology, Department of Medicine, University of Colorado Health Sciences Center, CO, USA
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  • R. W. McMurray

    1. Division of Rheumatology, G.V. (Sonny) Montgomery VAMC and Division of Rheumatology/Molecular Immunology, University of Mississippi Medical Center, Jackson, MS, USA and Division of Allergy and Immunology, Department of Medicine, University of Colorado Health Sciences Center, CO, USA
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Address reprint requests to Robert W. McMurray, Division of Rheumatology and Molecular Immunology, L525 Clinical Sciences Building, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. E-mail: robert.mcmurray@med.va.gov

Abstract

PROBLEM:  Pregnancy is characterized by dramatic immunologic changes most commonly characterized as suppression of cell-mediated immunity. Mechanisms of this immunosuppression are obscure but may be caused by increases in pregnancy-associated sex steroids such as 17-β-estradiol or progesterone.

METHOD OF STUDY:  Using five myelomonocytic cell lines in various stages of differentiation, the effects of 17-β-estradiol and progesterone on cell cycling, apoptosis, and bcl-2 expression in randomly cycling cells before and after lipopolysaccharide (LPS) activation were examined.

RESULTS:  Lipopolysaccharide alone inhibited cell cycle progression in THP-1 monocyte-like cells and U-937 histiocyte-like cells. Estrogen alone produced cell cycle arrest in all myelomonocytic cells except HL-60 pro-myelocyte-like cells. Progesterone had effects predominantly on pro-myelocytic-like HL-60 cells, inducing apoptosis. Estrogen and progesterone both decreased levels of bcl-2 in KG-1α, HL-60, and THP-1 cells. LPS partially antagonized both estrogen-induced THP-1 apoptosis and its suppression of bcl-2 protein.

CONCLUSIONS:  Sex steroid-induced effects on cell cycle transition and apoptosis are potential mechanisms by which pregnancy-induced cell-mediated immune suppression may occur. Further investigation should provide a better understanding of pregnancy-induced immune changes and, perhaps, sex-based differences in monocyte function and immunologic responses.

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