title: Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion.
abstract: A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported. In this study, we evaluated the effects of progesterone on rat dendritic cells (DCs) at ranges encompassing physiologic and pharmacologic concentrations to determine whether progesterone plays a role in modulating DC-mediated immune responses. DCs were derived by culturing rat bone marrow cells in granulocyte macrophage colony-stimulating factor and IL-4. Cells were analyzed for expression of PR using FACS analysis, real-time reverse transcriptase-PCR and fluorescent microscopy. Progesterone treatment of LPS-activated, mature bone marrow-derived dendritic cells (BMDCs) suppressed production of the pro-inflammatory response-promoting cytokines tumor necrosis factor-alpha and IL-1beta in a dose-dependent manner but did not affect production of the pro-inflammatory response-inhibiting cytokine IL-10. Treatment of cells with progesterone also resulted in down-regulation of co-stimulatory molecule CD80 and MHC class II molecule RT1B expression. In addition, progesterone inhibited DC-stimulated proliferation of T cells. Suppression of pro-inflammatory response-promoting cytokine production by progesterone was prevented using the PR antagonist RU486. There was no dose-dependent effect of progesterone treatment on immature DC capacity to take up antigenic peptide. These data indicate that progesterone directly inhibits mature rat BMDC capacity to drive pro-inflammatory responses. This mechanism could contribute to or account for some of the differential expression of autoimmune/inflammatory disease in females.
authors.affiliation: Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health/National Institutes of Health, 5625 Fishers Lane, Bethesda, MD 20892, USA.
authors.forename: Cherie L
authors.initials: CL
authors.lastname: Butts
authors.forename: Shetha A
authors.initials: SA
authors.lastname: Shukair
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Duncan
authors.forename: Eve
authors.initials: E
authors.lastname: Bowers
authors.forename: Cash
authors.initials: C
authors.lastname: Horn
authors.forename: Elena
authors.initials: E
authors.lastname: Belyavskaya
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tonelli
authors.forename: Esther M
authors.initials: EM
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008213:Lymphocyte Activation; D008856:Microscopy, Fluorescence; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011372:Progestins / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000941:Antigens; D018122:B7-1 Antigen; D006649:Histocompatibility Antigens; D006727:Hormone Antagonists; D053583:Interleukin-1beta; D011372:Progestins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; C038353:histocompatibility antigens RT, rat; D015735:Mifepristone; D011374:Progesterone