A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis

Halina Offner, Magdalena Polanczyk

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-β estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. The E2 mediates inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE are mediated through Esr-1 (α receptor for E2) but not Esr-2 (β receptor for E2), as are its anti-inflammatory and neuroprotective effects. A novel finding is that E2 upregulated the expression of FoxP3 that contributes to the activity of CD4 + CD25 + T regulatory cells (Treg). The protective effects of E2 in EAE suggest its use as a therapy for multiple sclerosis (MS). Possible risks may be minimized by using sub-pregnancy levels of exogenous E2 that produced synergistic effects when used in combination with another immunoregulatory therapy. Alternatively, one might envision using E2 derivatives alone or in combination therapies in both male and female MS patients.

Original languageEnglish (US)
Title of host publicationAnnals of the New York Academy of Sciences
Pages343-372
Number of pages30
Volume1089
DOIs
StatePublished - Nov 2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1089
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Autoimmune Experimental Encephalomyelitis
Neuroprotective Agents
Multiple Sclerosis
Estrogens
Derivatives
T-cells
Neurology
Estradiol
Anti-Inflammatory Agents
Cells
Cell Migration Inhibition
Hormones
Tissue
Nerve Tissue
Regulatory T-Lymphocytes
Myelin Sheath
Axons
Therapeutics
Central Nervous System
T-Lymphocytes

Keywords

  • EAE
  • Estrogen
  • Estrogen receptors
  • FoxP3
  • Immunoregulation
  • Multiple sclerosis
  • Neuroprotection
  • Treg

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Offner, H., & Polanczyk, M. (2006). A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. In Annals of the New York Academy of Sciences (Vol. 1089, pp. 343-372). (Annals of the New York Academy of Sciences; Vol. 1089). https://doi.org/10.1196/annals.1386.021

A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. / Offner, Halina; Polanczyk, Magdalena.

Annals of the New York Academy of Sciences. Vol. 1089 2006. p. 343-372 (Annals of the New York Academy of Sciences; Vol. 1089).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Offner, H & Polanczyk, M 2006, A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. in Annals of the New York Academy of Sciences. vol. 1089, Annals of the New York Academy of Sciences, vol. 1089, pp. 343-372. https://doi.org/10.1196/annals.1386.021
Offner H, Polanczyk M. A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. In Annals of the New York Academy of Sciences. Vol. 1089. 2006. p. 343-372. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1386.021
Offner, Halina ; Polanczyk, Magdalena. / A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis. Annals of the New York Academy of Sciences. Vol. 1089 2006. pp. 343-372 (Annals of the New York Academy of Sciences).
@inproceedings{551ca6513c014d24bbc801781e8d1cac,
title = "A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis",
abstract = "The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-β estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. The E2 mediates inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE are mediated through Esr-1 (α receptor for E2) but not Esr-2 (β receptor for E2), as are its anti-inflammatory and neuroprotective effects. A novel finding is that E2 upregulated the expression of FoxP3 that contributes to the activity of CD4 + CD25 + T regulatory cells (Treg). The protective effects of E2 in EAE suggest its use as a therapy for multiple sclerosis (MS). Possible risks may be minimized by using sub-pregnancy levels of exogenous E2 that produced synergistic effects when used in combination with another immunoregulatory therapy. Alternatively, one might envision using E2 derivatives alone or in combination therapies in both male and female MS patients.",
keywords = "EAE, Estrogen, Estrogen receptors, FoxP3, Immunoregulation, Multiple sclerosis, Neuroprotection, Treg",
author = "Halina Offner and Magdalena Polanczyk",
year = "2006",
month = "11",
doi = "10.1196/annals.1386.021",
language = "English (US)",
isbn = "1573316695",
volume = "1089",
series = "Annals of the New York Academy of Sciences",
pages = "343--372",
booktitle = "Annals of the New York Academy of Sciences",

}

TY - GEN

T1 - A potential role for estrogen in experimental autoimmune encephalomyelitis and multiple sclerosis

AU - Offner, Halina

AU - Polanczyk, Magdalena

PY - 2006/11

Y1 - 2006/11

N2 - The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-β estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. The E2 mediates inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE are mediated through Esr-1 (α receptor for E2) but not Esr-2 (β receptor for E2), as are its anti-inflammatory and neuroprotective effects. A novel finding is that E2 upregulated the expression of FoxP3 that contributes to the activity of CD4 + CD25 + T regulatory cells (Treg). The protective effects of E2 in EAE suggest its use as a therapy for multiple sclerosis (MS). Possible risks may be minimized by using sub-pregnancy levels of exogenous E2 that produced synergistic effects when used in combination with another immunoregulatory therapy. Alternatively, one might envision using E2 derivatives alone or in combination therapies in both male and female MS patients.

AB - The extensive literature and the work from our laboratory illustrate the large number of complex processes affected by estrogen that might contribute to the striking ability of 17-β estradiol (E2) and its derivatives to inhibit clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in mice. These effects require sustained exposure to relatively low doses of exogenous hormone and offer better protection when initiated prior to induction of EAE. The E2 mediates inhibition of encephalitogenic T cells, inhibition of cell migration into central nervous system tissue, and neuroprotective effects that promote axon and myelin survival. E2 effects on EAE are mediated through Esr-1 (α receptor for E2) but not Esr-2 (β receptor for E2), as are its anti-inflammatory and neuroprotective effects. A novel finding is that E2 upregulated the expression of FoxP3 that contributes to the activity of CD4 + CD25 + T regulatory cells (Treg). The protective effects of E2 in EAE suggest its use as a therapy for multiple sclerosis (MS). Possible risks may be minimized by using sub-pregnancy levels of exogenous E2 that produced synergistic effects when used in combination with another immunoregulatory therapy. Alternatively, one might envision using E2 derivatives alone or in combination therapies in both male and female MS patients.

KW - EAE

KW - Estrogen

KW - Estrogen receptors

KW - FoxP3

KW - Immunoregulation

KW - Multiple sclerosis

KW - Neuroprotection

KW - Treg

UR - http://www.scopus.com/inward/record.url?scp=33847791448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847791448&partnerID=8YFLogxK

U2 - 10.1196/annals.1386.021

DO - 10.1196/annals.1386.021

M3 - Conference contribution

C2 - 17261780

AN - SCOPUS:33847791448

SN - 1573316695

SN - 9781573316699

VL - 1089

T3 - Annals of the New York Academy of Sciences

SP - 343

EP - 372

BT - Annals of the New York Academy of Sciences

ER -