Cited by 80Estrogen and related hormone effectsImmune cells in cancerWound Healing and Treatments

Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge

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Pepe, Giovanna, Braga, Daniele, Renzi, Tiziana A., Villa, Alessandro, Bolego, Chiara, D’Avila, Francesca, Barlassina, Cristina, Maggi, Adriana +2 more·2017·Scientific Reports

Abstract

Beyond the physiology of reproduction, estrogen controls the homeostasis of several tissues. Although macrophages play a key role in tissue remodeling, the interplay with estrogen is still ill defined. Using a transcriptomic approach we first obtained a comprehensive list of genes that are differentially expressed in peritoneal macrophages in response to physiological levels of 17β-estradiol (E 2 ) injected in intact female mice. Our data also showed the dynamic nature of the macrophage response to E 2 and pointed to specific biological programs induced by the hormone, with cell proliferation, immune response and wound healing being the most prominent functional categories. Indeed, the exogenous administration of E 2 and, more importantly, the endogenous hormonal surge proved to support macrophage proliferation in vivo , as shown by cell cycle gene expression, BrdU incorporation and cell number. Furthermore, E 2 promoted an anti-inflammatory and pro-resolving macrophage phenotype, which converged on the induction of genes related to macrophage alternative activation and on IL-10 expression in vivo . Hormone action was maintained in an experimental model of peritoneal inflammation based on zymosan injection. These findings highlight a direct effect of estrogen on macrophage expansion and phenotypic adaptation in homeostatic conditions and suggest a role for this interplay in inflammatory pathologies.

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Authors
Pepe, G., Braga, D., Renzi, T. A., Villa, A., Bolego, C., D’Avila, F., Barlassina, C., Maggi, A., Locati, M., & Vegeto, E.
Affiliations
  • University of Milan (IT)
  • University of Padua (IT)
Corresponding author
Vegeto, Elisabetta
Venue
Scientific Reports
Published
2017-03-20
Volume
7
Issue
1
Pages
44270-44270
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2599883686
Cited by
80
References
64
Citations by year
2026: 5 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 16 · 2021: 11 · 2020: 11 · 2019: 3 · 2018: 9 · 2017: 4 · 2016: 1
FWCI
4.90
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
Funders
  • European Commission (2007–2013, FP7 2007-2013, 281608, FP7/2007, 278850)
  • Fondazione Cariplo (2011-0591)
  • Associazione Italiana per la Ricerca sul Cancro (IG 2013)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
estrogen, estradiol, macrophages, peritoneal macrophages, macrophage self-renewal, phenotypic conversion, macrophage proliferation, alternative macrophage activation, IL-10, peritonitis, zymosan, tissue homeostasis, cell cycle genes
MeSH terms
Angiopoietin-Like Protein 4, Animals, Arginase, Estradiol, Female, Gene Expression Regulation, Immunity, Innate, Macrophage Activation, Mice, Inbred C57BL, Ovariectomy, Peritonitis, Phenotype, Zymosan, Interleukin-10, Macrophages, Peritoneal, Cell Cycle Proteins, Gene Expression Profiling, Vascular Endothelial Growth Factor A, Cell Proliferation, Mice, Transcriptome

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