دورية أكاديمية
Low-dose 17α-ethinyl estradiol (EE) exposure exacerbates lupus renal disease and modulates immune responses to TLR7/9 agonists in genetically autoimmune-prone mice.
| العنوان: | Low-dose 17α-ethinyl estradiol (EE) exposure exacerbates lupus renal disease and modulates immune responses to TLR7/9 agonists in genetically autoimmune-prone mice. |
|---|---|
| المؤلفون: | Edwards MR; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Dai R; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Heid B; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Cowan C; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Werre SR; Population Health Sciences, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Cecere T; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA., Ahmed SA; Infectious Disease Research Facility (IDRF), Department of Biomedical Sciences and Pathobiology, VA-MD College of Vet. Medicine, Virginia Tech, Blacksburg, VA, USA. ansrahmd@vt.edu. |
| المصدر: | Scientific reports [Sci Rep] 2020 Mar 23; Vol. 10 (1), pp. 5210. Date of Electronic Publication: 2020 Mar 23. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Ethinyl Estradiol/*toxicity , Immune Complex Diseases/*immunology , Lupus Nephritis/*immunology , Membrane Glycoproteins/*agonists , Toll-Like Receptor 7/*agonists , Toll-Like Receptor 9/*agonists, Animals ; Autoantibodies/analysis ; Blood Urea Nitrogen ; Creatinine/blood ; Cytokines/biosynthesis ; Ethinyl Estradiol/administration & dosage ; Female ; Imiquimod/pharmacology ; Immune Complex Diseases/chemically induced ; Immune Complex Diseases/drug therapy ; Immune Complex Diseases/genetics ; Immunoglobulin G/analysis ; Kidney Glomerulus/immunology ; Kidney Glomerulus/pathology ; Leukocytes/metabolism ; Lupus Nephritis/chemically induced ; Lupus Nephritis/drug therapy ; Mice ; Mice, Inbred MRL lpr ; Proteinuria/etiology ; Spleen/pathology |
| مستخلص: | 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. |
| References: | Mol Reprod Dev. 2015 Jul-Aug;82(7-8):518-29. (PMID: 26153368) Annu Rev Immunol. 1991;9:243-69. (PMID: 1910678) J Immunol. 2010 Feb 15;184(4):1840-8. (PMID: 20089701) Mol Cell Endocrinol. 2015 Nov 5;415:45-55. (PMID: 26277401) Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2703-8. (PMID: 10694576) Immunol Rev. 2019 Mar;288(1):136-148. (PMID: 30874345) Arthritis Rheum. 1997 May;40(5):804-8. (PMID: 9153539) J Autoimmun. 2010 Jun;34(4):339-48. (PMID: 19944565) Iran J Allergy Asthma Immunol. 2016 Jun;15(3):229-36. (PMID: 27424138) J Exp Med. 1982 Jun 1;155(6):1690-701. (PMID: 7077223) J Am Soc Nephrol. 2003 Feb;14(2):317-26. (PMID: 12538732) Endocrinology. 2019 Jan 1;160(1):101-118. (PMID: 30418530) Arthritis Rheum. 1995 Oct;38(10):1492-9. (PMID: 7575699) J Immunol. 2007 Aug 1;179(3):1776-83. (PMID: 17641044) PLoS One. 2010 Dec 10;5(12):e14302. (PMID: 21170274) J Am Soc Nephrol. 2006 Jan;17(1):141-9. (PMID: 16280469) Arthritis Rheum. 2007 Apr;56(4):1251-62. (PMID: 17393454) Arthritis Rheum. 2009 Apr 15;61(4):476-81. (PMID: 19333988) Sci Rep. 2020 Mar 23;10(1):5210. (PMID: 32251357) Curr Opin Rheumatol. 2012 Jul;24(4):383-8. (PMID: 22504579) Int Immunol. 2017 Jun 1;29(6):263-276. (PMID: 28637300) CNS Neurosci Ther. 2014 Aug;20(8):787-90. (PMID: 24931054) PLoS One. 2017 Feb 13;12(2):e0172105. (PMID: 28192517) Autoimmune Dis. 2014;2014:743616. (PMID: 24804084) J Autoimmun. 1993 Jun;6(3):265-79. (PMID: 8397711) J Clin Invest. 2016 Apr 1;126(4):1525-37. (PMID: 26999605) Arthritis Rheum. 2001 May;44(5):1122-6. (PMID: 11352244) Environ Health Perspect. 1999 Oct;107 Suppl 5:681-6. (PMID: 10502531) Medicine (Baltimore). 2015 May;94(17):e794. (PMID: 25929930) Am J Pathol. 1982 Feb;106(2):300-2. (PMID: 6978075) Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772) J Clin Invest. 1998 Jan 15;101(2):364-71. (PMID: 9435308) Sci Rep. 2017 Aug 11;7(1):7970. (PMID: 28801669) Am J Reprod Immunol. 2003 Mar;49(3):129-38. (PMID: 12797519) J Am Assoc Lab Anim Sci. 2013 Mar;52(2):130-41. (PMID: 23562095) Biol Sex Differ. 2013 Nov 01;4(1):19. (PMID: 24175965) J Autoimmun. 2010 Dec;35(4):291-8. (PMID: 20810248) Immunopharmacol Immunotoxicol. 2017 Feb;39(1):11-18. (PMID: 28049380) Nat Commun. 2018 May 1;9(1):1758. (PMID: 29717110) Clin Immunol Immunopathol. 1985 Nov;37(2):220-9. (PMID: 4042431) Viruses. 2012 Dec;4(12):3701-30. (PMID: 23342374) Toxicology. 2000 Sep 7;150(1-3):191-206. (PMID: 10996675) Environ Health Perspect. 2010 Mar;118(3):338-44. (PMID: 20194073) Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1497-502. (PMID: 24474776) J Immunol. 2013 May 15;190(10):4982-90. (PMID: 23589617) Eur J Immunol. 2010 Sep;40(9):2549-56. (PMID: 20623549) Adv Immunol. 1985;37:269-390. (PMID: 3890479) Immunity. 2018 Oct 16;49(4):725-739.e6. (PMID: 30314758) Clin Immunol. 2004 Dec;113(3):224-30. (PMID: 15507385) PLoS One. 2016 Apr 12;11(4):e0153509. (PMID: 27070142) Blood. 2008 Dec 1;112(12):4591-7. (PMID: 18791161) J Exp Med. 1978 Nov 1;148(5):1198-215. (PMID: 309911) Sci Rep. 2017 Apr 12;7(1):856. (PMID: 28404993) Clin Immunol Immunopathol. 1980 Mar;15(3):258-78. (PMID: 6445246) Autoimmun Rev. 2012 May;11(6-7):A502-14. (PMID: 22193289) Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834) J Immunol. 2009 Dec 1;183(11):6998-7005. (PMID: 19890039) Front Immunol. 2016 Jan 06;6:635. (PMID: 26779182) J Autoimmun. 1989 Aug;2(4):543-52. (PMID: 2789656) |
| معلومات مُعتمدة: | T32 OD010430 United States OD NIH HHS |
| المشرفين على المادة: | 0 (Autoantibodies) 0 (Cytokines) 0 (Immunoglobulin G) 0 (Membrane Glycoproteins) 0 (Tlr7 protein, mouse) 0 (Tlr9 protein, mouse) 0 (Toll-Like Receptor 7) 0 (Toll-Like Receptor 9) 423D2T571U (Ethinyl Estradiol) AYI8EX34EU (Creatinine) P1QW714R7M (Imiquimod) |
| تواريخ الأحداث: | Date Created: 20200407 Date Completed: 20201130 Latest Revision: 20240329 |
| رمز التحديث: | 20240329 |
| مُعرف محوري في PubMed: | PMC7090002 |
| DOI: | 10.1038/s41598-020-62124-6 |
| PMID: | 32251357 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder كن أول من يترك تعليقا!