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, Halina Offner

Research output: Contribution to journalArticle

Abstract

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-(Esr1) and -β (Esr2) genes. We demonstrate that the protective effect of E2 is abrogated in B6.129-Esr1tm1Unc 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-α, 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.

Original languageEnglish (US)
Pages (from-to)1599-1605
Number of pages7
JournalAmerican Journal of Pathology
Volume163
Issue number4
StatePublished - Oct 1 2003
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Estrogen Receptors
Estradiol
Cytokine Receptors
Chemokine Receptors
Serum
Chemokines
Multiple Sclerosis
Interleukin-6
Estrogens
Clinical Trials
Peptides
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Polanczyk, M., Zamora, A., Subramanian, S., Matejuk, A., Hess, D. L., Blankenhorn, E. P., ... Offner, H. (2003). The protective effect of 17β-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-α. American Journal of Pathology, 163(4), 1599-1605.

The protective effect of 17β-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-α. / Polanczyk, Magdalena; Zamora, Alex; Subramanian, Sandhya; Matejuk, Agata; Hess, David L.; Blankenhorn, Elizabeth P.; Teuscher, Cory; Vandenbark, Arthur A.; Offner, Halina.

In: American Journal of Pathology, Vol. 163, No. 4, 01.10.2003, p. 1599-1605.

Research output: Contribution to journalArticle

Polanczyk, M, Zamora, A, Subramanian, S, Matejuk, A, Hess, DL, Blankenhorn, EP, Teuscher, C, Vandenbark, AA & Offner, H 2003, 'The protective effect of 17β-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-α', American Journal of Pathology, vol. 163, no. 4, pp. 1599-1605.
Polanczyk M, Zamora A, Subramanian S, Matejuk A, Hess DL, Blankenhorn EP et al. The protective effect of 17β-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-α. American Journal of Pathology. 2003 Oct 1;163(4):1599-1605.
Polanczyk, Magdalena ; Zamora, Alex ; Subramanian, Sandhya ; Matejuk, Agata ; Hess, David L. ; Blankenhorn, Elizabeth P. ; Teuscher, Cory ; Vandenbark, Arthur A. ; Offner, Halina. / The protective effect of 17β-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-α. In: American Journal of Pathology. 2003 ; Vol. 163, No. 4. pp. 1599-1605.
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