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The Protective Effect of 17β-Estradiol on Experimental Autoimmune Encephalomyelitis Is Mediated through Estrogen Receptor-α
Journal article   Open access   Peer reviewed

The Protective Effect of 17β-Estradiol on Experimental Autoimmune Encephalomyelitis Is Mediated through Estrogen Receptor-α

Magdalena Polanczyk, Alex Zamora, Sandhya Subramanian, Agata Matejuk, David L Hess, Elizabeth P Blankenhorn, Cory Teuscher, Arthur A Vandenbark and Halina Offner
The American journal of pathology, v 163(4), pp 1599-1605
Oct 2003
DOI: https://doi.org/10.1016/S0002-9440(10)63516-X
PMID: 14507666
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/s0002-9440(10)63516-xView
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Regular
Low-dose estrogen (E2) treatment significantly inhibits the clinical signs and histopathological lesions of experimental autoimmune encephalomyelitis (EAE), and is being used in clinical trials to treat multiple sclerosis. To assess the role of intracytoplasmic estrogen receptors in mediating suppression of EAE, we studied mice with disrupted estrogen receptor-α ( Esr1 ) and -β ( Esr2 ) genes. We demonstrate that the protective effect of E2 is abrogated in B6.129- Esr1 tm1Unc mice ( Esr1 −/−) but not in B6.129- Esr2 tm1Unc mice ( Esr2 −/−). The loss of E2-mediated protection from EAE in Esr1 −/− mice immunized with the encephalitogenic MOG-35–55 peptide was manifested phenotypically by the development of severe acute clinical signs and histopathological lesions even in the presence of moderately high serum E2 levels. This is in contrast to C57BL/6 wild-type (WT) mice and Esr2 −/− mice in which E2 treatment resulted in comparable serum levels and markedly suppressed clinical signs of EAE and abolished inflammatory lesions in the CNS. This pattern showing a lack of E2-dependent inhibition of EAE in Esr1 −/− mice was mirrored by an enhanced rather than a reduced secretion of TNF-α, IFN-γ, and interleukin (IL)-6 in MOG-specific splenocytes and a lack of inhibition of message for inflammatory cytokines, chemokines and chemokine receptors in CNS tissue. These results indicate that the immunomodulatory effects of E2 in EAE are dependent on Esr1 and not Esr2 signaling.

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Pathology
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