17β-estradiol inhibits cytokine, chemokine, and chemokine receptor mRNA expression in the central nervous system of female mice with experimental autoimmune encephalomyelitis

Agata Matejuk, Kirsten Adlard, Alex Zamora, Marc Silverman, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Cytokines and chemokines govern leukocyte trafficking, thus regulating inflammatory responses. In this study, the anti-inflammatory effects of low dose 17β-estradiol were evaluated on chemokine, chemokine receptor, and cytokine expression in the spinal cords (SC) of BV8S2 transgenic female mice during acute and recovery phases of experimental autoimmune encephalomyelitis (EAE). In EAE protected mice, 17β-estradiol strongly inhibited mRNA expression of the chemokines RANTES, MIP-1α, MIP-2, IP-10, and MCP-1, and of the chemokine receptors CCR1, CCR2 and CCR5 at both time points. Conversely, ovariectomy, which abrogated basal 17β-estradiol levels and increased the severity of EAE, enhanced the expression of MIP-1α and MIP-2 that were over-expressed by inflammatory mononuclear cells in SC. 17β-estradiol inhibited expression of LT-β, TNF-α, and IFN-γ in SC, but had no effect on IL-4 or IL-10, indicating reduced inflammation but no deviation toward a Th2 response. Interestingly, elevated expression of CCR1 and CCR5 by lymph node cells was also inhibited in 17β-estradiol treated mice with EAE. Low doses of 17β-estradiol added in vitro to lymphocyte cultures had no direct effect on the activation of MBP-Ac1-11 specific T cells, and only at high doses diminished production of IFN-γ but not IL-12 or IL-10. These results suggest that the beneficial effects of 17β-estradiol are mediated in part by strong inhibition of recruited inflammatory cells, resulting in reduced production of inflammatory chemokines and cytokines in CNS, with modest effects on encephalitogenic T cells that seem to be relatively 17β-estradiol insensitive.

Original languageEnglish (US)
Pages (from-to)529-542
Number of pages14
JournalJournal of Neuroscience Research
Volume65
Issue number6
DOIs
StatePublished - Sep 15 2001

Keywords

  • 17β-estradiol
  • Autoimmunity
  • Chemokines
  • Cytokines
  • EAE/MS

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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