T Thongngarm1, J K Jenkins, K Ndebele, R W McMurray. 1. Division of Rheumatology, G.V. (Sonny) Montgomery VAMC, University of Mississippi Medical Center, Jackson, MS 39216, USA.
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-beta-estradiol or progesterone. METHOD OF STUDY: 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.
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-beta-estradiol or progesterone. METHOD OF STUDY: 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.
Authors: Gwen E Dressing; Jodi E Goldberg; Nathan J Charles; Kathryn L Schwertfeger; Carol A Lange Journal: Steroids Date: 2010-09-24 Impact factor: 2.668
Authors: Ruixin Hao; Maria Bondesson; Amar V Singh; Anne Riu; Catherine W McCollum; Thomas B Knudsen; Daniel A Gorelick; Jan-Åke Gustafsson Journal: PLoS One Date: 2013-11-06 Impact factor: 3.240