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Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis
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Greaves, Erin, Temp, Julia, Esnal-Zufiurre, Arantza, Mechsner, Sylvia, Horne, Andrew W. and Saunders, Philippa T.K. (2015) Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis. The American Journal of Pathology, 185 (8). pp. 2286-2297. doi:10.1016/j.ajpath.2015.04.012 ISSN 00029440.
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Official URL: http://dx.doi.org/10.1016/j.ajpath.2015.04.012
Abstract
Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor beta, with up to 20% being estrogen receptor alpha positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1-differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key rote for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Journal or Publication Title: | The American Journal of Pathology | ||||||
Publisher: | Elsevier | ||||||
ISSN: | 00029440 | ||||||
Official Date: | 11 June 2015 | ||||||
Dates: |
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Volume: | 185 | ||||||
Number: | 8 | ||||||
Page Range: | pp. 2286-2297 | ||||||
DOI: | 10.1016/j.ajpath.2015.04.012 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||
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