title: High Physiological Concentrations of Progesterone Reverse Estradiol-Mediated Changes in Differentiation and Functions of Bone Marrow Derived Dendritic Cells.
abstract: Female sex steroids, estradiol (E2) and progesterone (P4), play a key role in regulating immune responses in women, including dendritic cell (DC) development, and functions. Although the two hormones co-occur in the body of women throughout the reproductive years, no studies have explored their complex combinatorial effects on DCs, given their ability to regulate each other's actions. We examined murine bone marrow derived dendritic cells (BMDC) differentiation and functions, in the presence of a wide range of physiological concentrations of each hormone, as well as the combination of the two hormones. E2 (10(-12) to 10(-8)M) enhanced the differentiation of CD11b+CD11c+ DCs from BM precursor cells, and promoted the expression of CD40 and MHC Class-II, in a dose-dependent manner. In contrast, P4 (10(-9) to 10(-5)M) inhibited DC differentiation, but only at the highest concentrations. These effects on BMDCs were observed both in the presence or absence of LPS. When both hormones were combined, higher concentrations of P4, at levels seen in pregnancy (10(-6)M) reversed the E2 effects, regardless of the concentration of E2, especially in the absence of LPS. Functionally, antigen uptake was decreased and pro-inflammatory cytokines, IL-12, IL-1 and IL-6 production by CD11b+CD11c+ DCs, was increased in the presence of E2 and these effects were reversed by high concentrations of P4. Our results demonstrate the distinct effects of E2 and P4 on differentiation and functions of bone marrow myeloid DCs. The dominating effect of higher physiological concentrations of P4 provides insight into how DC functions could be modulated during pregnancy.
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Fangming
authors.initials: F
authors.lastname: Xiu
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Varun C
authors.initials: VC
authors.lastname: Anipindi
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Philip V
authors.initials: PV
authors.lastname: Nguyen
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Boudreau
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Denis P
authors.initials: DP
authors.lastname: Snider
authors.affiliation: McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, Ontario, Canada L8N 3Z5.
authors.forename: Charu
authors.initials: C
authors.lastname: Kaushic
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D004967:Estrogens; D011372:Progestins; D011374:Progesterone; D004958:Estradiol