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Cited by 103Estrogen and related hormone effectsImmune Response and InflammationNeuroinflammation and Neurodegeneration Mechanisms

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

Vegeto, Elisabetta, Ghisletti, Serena, Meda, Clara, Etteri, Sabrina, Belcredito, Silvia, Maggi, Adriana·2004·The Journal of Steroid Biochemistry and Molecular Biology
DOI 10.1016/j.jsbmb.2004.02.004
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Abstract

We have previously shown that 17beta-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 alpha-isoform of the estrogen receptor (ERalpha) and not ERbeta. 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 ERalpha 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.

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  • Short-duration E2 treatment (2-6 hours) has an anti-inflammatory effect, while chronic administration over 60 days is associated with a pro-inflammatory response.

    “Similarly, a short duration of E2 treatment (2–6 hours) has an anti-inflammatory effect [78, 79], while chronic administration over 60 days is associated with a pro-inflammatory response [77].”

    From Estrogen and thrombosis: a bench to bedside review (2020) · cites this paper as [79]

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Authors
Vegeto, E., Ghisletti, S., Meda, C., Etteri, S., Belcredito, S., & Maggi, A.
Affiliations
University of Milan (IT)
Corresponding author
Maggi, Adriana
ORCID
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2004-06
Volume
91
Issue
1-2
Pages
59-66
ISSN
0960-0760 (ISSN-L)
DOI
10.1016/j.jsbmb.2004.02.004
OpenAlex
W1989736409
Cited by
103
References
40
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 5
FWCI
4.98
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
estradiol, lipopolysaccharide, macrophages, RAW 264.7 macrophages, estrogen receptor alpha, estrogen receptor beta, microglia, anti-inflammatory activity, MMP-9, TLR4, CD14, endotoxin signaling, pro-inflammatory gene expression
MeSH terms
Animals, Animals, Newborn, Brain, Cell Line, Cells, Cultured, Enzyme Activation, Estradiol, Estrogens, Gene Expression Regulation, Lipopolysaccharides, Macrophages, Membrane Glycoproteins, Microscopy, Fluorescence, Receptors, Cell Surface, Receptors, Estrogen, Time Factors, Signal Transduction, Polymerase Chain Reaction, Rats, Sprague-Dawley, Microglia, DNA, Complementary, Lipopolysaccharide Receptors, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Matrix Metalloproteinase 9, Estrogen Receptor alpha, Estrogen Receptor beta, Toll-Like Receptors, Toll-Like Receptor 4, Mice, Rats

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