Low-dose 17α-ethinyl estradiol (EE) exposure exacerbates lupus renal disease and modulates immune responses to TLR7/9 agonists in genetically autoimmune-prone mice
| dc.contributor.author | Edwards, Michael R. | en |
| dc.contributor.author | Dai, Rujuan | en |
| dc.contributor.author | Heid, Bettina | en |
| dc.contributor.author | Cowan, Catharine | en |
| dc.contributor.author | Werre, Stephen R. | en |
| dc.contributor.author | Cecere, Thomas E. | en |
| dc.contributor.author | Ahmed, Sattar Ansar | en |
| dc.date.accessioned | 2020-08-06T17:58:47Z | en |
| dc.date.available | 2020-08-06T17:58:47Z | en |
| dc.date.issued | 2020 | en |
| dc.description.abstract | Estrogens have been shown to regulate the immune system and modulate multiple autoimmune diseases. 17α-ethinyl estradiol (EE), a synthetic analog of 17β-estradiol, is prescribed commonly and found in oral contraceptives and hormone replacement therapies. Surprisingly, few studies have investigated the immunoregulatory effects of exposure to EE, especially in autoimmunity. In this study, we exposed autoimmune-prone female MRL/lpr mice to a human-relevant dose of EE through the oral route of exposure. Since lupus patients are prone to infections, groups of mice were injected with viral (Imiquimod, a TLR7 agonist) or bacterial (ODN 2395, a TLR9 agonist) surrogates. We then evaluated autoimmune disease parameters, kidney disease, and response to in vivo TLR7/9 pathogenic signals. EE-exposed mice had increased proteinuria as early as 7 weeks of age. Proteinuria, blood urea nitrogen, and glomerular immune complex deposition were also exacerbated when compared to controls. Production of cytokines by splenic leukocytes were altered in EE-exposed mice. Our study shows that oral exposure to EE, even at a very low dose, can exacerbate azotemia, increase clinical markers of renal disease, enhance glomerular immune complex deposition, and modulate TLR7/9 cytokine production in female MRL/lpr mice. This study may have implications for EE-exposure risk for genetically lupus-prone individuals. | en |
| dc.description.sponsorship | Preparation of this publication was supported by the Virginia-Maryland College of Veterinary Medicine (VMCVM) Intramural Research Competition (IRC) Grant (grant number 175185); AH&D USDA-NIFA grant (1016123), Interdepartmental funds to SAA, and by the National Institute of Health T32 training grant (grant number 5T32OD010430-09). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or VMCVM. We would like to acknowledge Virginia Tech’s OASF financial support for publication. | en |
| dc.format.extent | 12 pages | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1038/s41598-020-62124-6 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/99583 | en |
| dc.identifier.volume | 10 | en |
| dc.language.iso | en | en |
| dc.publisher | Springer Nature | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.title | Low-dose 17α-ethinyl estradiol (EE) exposure exacerbates lupus renal disease and modulates immune responses to TLR7/9 agonists in genetically autoimmune-prone mice | en |
| dc.title.serial | Scientific Reports | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |
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