Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad, D. and Salehipour, Z. and Nosratabadi, R. and Rastin, M. and Kokhaei, P. and Mahmoudi, M. B. and Amini, A. A. and Mahmoudi, M. (2016) Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice. Journal of Immunotoxicology, 13 (6). pp. 885-896.

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Abstract

Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased TH2 and Treg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-β, but concurrently resulted in a significant reduction in production of interferon (IFN)-γ, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of TH1 and TH17 cells, as well as significant increase in percentages of Treg and TH2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high- and medium-dose estrogen treatments reduced T-bet and ROR-γt factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen–similar to a pregnancy level of estrogen–could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Item Type: Article
Additional Information: Cited By :12 Export Date: 16 February 2020 Correspondence Address: Mahmoudi, M.; Department of Immunology and Allergy, School of Medicine, Immunology Research Center, BuAli Research Institute, Mashhad University of Medical SciencesIran; email: mahmoudim@mums.ac.ir
Uncontrolled Keywords: central nervous system EAE Estrogen multiple sclerosis transcription factor gamma interferon interleukin 10 interleukin 17 interleukin 23 interleukin 4 interleukin 6 retinoid related orphan receptor gamma transcription factor FOXP3 transcription factor GATA 3 transforming growth factor beta cytokine animal experiment animal model animal tissue Article CD4+ T lymphocyte controlled study cytokine release disease severity down regulation drug megadose enzyme linked immunosorbent assay estrogen blood level estrogen therapy experimental autoimmune encephalomyelitis female flow cytometry histopathology low drug dose lymphocyte proliferation lymphocytic infiltration mouse nonhuman ovariectomy priority journal protein expression real time polymerase chain reaction T lymphocyte Th1 cell Th17 cell treatment duration animal C57BL mouse cell culture dose calculation genetics human immunological tolerance immunology metabolism pregnancy regulatory T lymphocyte Th2 cell Animals Cells, Cultured Cytokines Drug Dosage Calculations Encephalomyelitis, Autoimmune, Experimental Estrogens Humans Immune Tolerance Mice Mice, Inbred C57BL T-Lymphocytes, Regulatory Th2 Cells Transcription Factors
Subjects: WP Gynecology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 02 Mar 2020 08:59
Last Modified: 02 Mar 2020 08:59
URI: http://eprints.mums.ac.ir/id/eprint/13017

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