Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge
Open accessAbstract
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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Estrogen is important to wound healing, and its deficiency delays or impairs wound healing.
“Numerous studies have shown that estrogen is important to wound healing, and its deficiency delays or impairs wound healing29–33.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [32]
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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
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-03-20
- Volume
- 7
- Issue
- 1
- Pages
- 44270-44270
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5357836
- 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
- gold
- doi.org
- 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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