Regulation of the lipopolysaccharide signal transduction pathway by 17β-estradiol in macrophage cells

Elisabetta Vegeto, Serena Ghisletti, Clara Meda, Sabrina Etteri, Silvia Belcredito, Adriana Maggi

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously shown that 17β-estradiol (E2) prevents the activation of brain macrophages, i.e. microglia cells, both in vitro and in vivo. Hormone exerts this inhibitory effect by inhibiting pro-inflammatory gene expression. In this study we further investigated on the molecular mechanism of E2 action in the RAW 264.7 macrophage cell line. We show here that these cells express the α-isoform of the estrogen receptor (ERα) and not ERβ. Similarly to its activity in brain macrophages, E2 is able to inhibit the activation program induced by lipopolysaccharide (LPS) in RAW 264.7 cells, as shown by the inhibitory effect of hormone on the morphological conversion and matrix metalloproteinase-9 (MMP-9) expression induced by the endotoxin. In addition, we demonstrate that hormone treatment is not associated with a reduction in the steady-state expression of Toll-like receptor-4 (TLR-4) and CD14, two components of the LPS receptor complex. Our results further confirm the anti-inflammatory role of ERα in macrophages and propose that the mechanism of hormone action on macrophage reactivity involves signaling molecules which are down-stream effectors of the LPS membrane receptors.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume91
Issue number1-2
DOIs
Publication statusPublished - Jun 2004

Keywords

  • CD14
  • Estrogen receptor-alpha
  • Expression
  • Microglia
  • MMP-9
  • RAW cells
  • TLR-4

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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