title: Immunomodulation by the estrogen metabolite 2-methoxyestradiol.
abstract: 2-methoxyestradiol (2me2), a metabolite of 17β-estradiol (E2), has been tested in phase II clinical cancer trials and models of inflammation. Its effects are only partly clarified. We investigated the effects of 2me2 on the immune system, using ovariectomized or sham-operated mice treated with a high and a low dose of 2me2 (2me2H and 2me2L), E2 or vehicle. We investigated antagonism of tissue proliferation and estrogen response element (ERE) activation. Established immunomodulation by E2 was reproduced. 2me2L increased NK and T-cells from bone marrow, spleen and liver. Both 2me2H and E2 induced uterus proliferation in ovariectomized mice, but no antagonistic effects on uteri growth were seen in intact animals. Both E2 and 2me2H activated EREs. Immunomodulation by 2me2 is tissue-, and concentration dependent. E2 regulated the immune system more potently. The higher dose of 2me2 resulted in E2 like effects, important to consider when developing 2me2 as a drug.
authors.affiliation: Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: alexandra.stubelius@rheuma.gu.se.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Stubelius
authors.affiliation: Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: malin.erlandsson@rheuma.gu.se.
authors.forename: Malin C
authors.initials: MC
authors.lastname: Erlandsson
authors.affiliation: Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: ulrika.islander@rheuma.gu.se.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.affiliation: Centre for Bone and Arthritis Research (CBAR), Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: hans.carlsten@rheuma.gu.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol; D000077584:2-Methoxyestradiol
keywords: 17β-Estradiol; 2-Methoxyestradiol; Estrogen response elements; Immune regulation; Immune system; Uterus proliferation