Estrogen and progesterone modulate monocyte cell cycle progression and apoptosis.
OBJECTIVE
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-beta-estradiol or progesterone.


METHODS
Using five myelomonocytic cell lines in various stages of differentiation, the effects of 17-beta-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-1alpha, 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.
Thongngarm
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T
Division of Rheumatology, G.V. (Sonny) Montgomery VAMC, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Jenkins
J K
JK
Ndebele
K
K
McMurray
R W
RW
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D020014:K562 Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011959:Receptors, Estradiol / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells
D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D011959:Receptors, Estradiol; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol