title: Estrogen inhibits systemic T cell expression of TNF-alpha and recruitment of TNF-alpha(+) T cells and macrophages into the CNS of mice developing experimental encephalomyelitis.
abstract: Estrogen treatment has been found to have suppressive activity in several models of autoimmunity. To investigate the mechanism of 17 beta-estradiol (E2) suppression of experimental autoimmune encephalomyelitis, we evaluated E2 effects on TNF-alpha expression in the central nervous system (CNS) and spleen of C57BL/6 mice immunized with MOG 35-55/CFA. Kinetic analysis demonstrated that E2 treatment drastically decreased the recruitment of total inflammatory cells as well as TNF-alpha(+) macrophages and T cells into the CNS at disease onset. In contrast, E2 had only moderate effects on the relatively high constitutive TNF-alpha expression by resident CNS microglial cells. E2 treatment also had profound inhibitory effects on expression of TNF-alpha by splenic CD4(+) T cells, including those responsive to MOG 35-55 peptide. We propose that the mechanism of E2 protection may involve both systemic inhibition of TNF-alpha expression and local (CNS) recruitment of inflammatory cells, with modest effects on TNF-alpha expression by resident CNS microglial cells.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, Oregon 97201, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ito
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Buenafe
authors.forename: Agata
authors.initials: A
authors.lastname: Matejuk
authors.forename: Alex
authors.initials: A
authors.lastname: Zamora
authors.forename: Marc
authors.initials: M
authors.lastname: Silverman
authors.forename: Jami
authors.initials: J
authors.lastname: Dwyer
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D004958:Estradiol