Dai R, Edwards M, Heid B and Ahmed SA
Endocrinology. 2019 Jan 1;160(1):101-118
17α-Ethinyl estradiol (EE), a synthetic analog of natural estrogen 17β-estradiol (E2), is extensively used in hormonal contraceptives and estrogen replacement therapy, and it has also been found in sewage effluents. Given that E2 is a well-known immunomodulator, surprisingly there has been only limited information on the cellular and molecular immunologic consequences of exposure to EE. To address this fundamental gap, we directly compared the effects of EE with E2 on splenic leukocytes of New Zealand Black × New Zealand White F1 progeny (NZB/WF1) mice during the preautoimmune period. We found that EE and E2 have common, as well as distinctive, immunologic effects, with EE exposure resulting in more profound effects. Both EE and E2 increased numbers of splenic neutrophils, enhanced neutrophil serine proteases and myeloperoxidase expression, promoted the production of nitric oxide and monocyte chemoattractant protein-1, and altered adaptive immune T cell subsets. However, activation of splenic leukocytes through the T cell receptor or Toll-like receptor (TLR)4 revealed not only common (IL-10), but also hormone-specific alterations of cytokines (IFNγ, IL-1β, ΤΝFα, IL-2). Furthermore, in EE-exposed mice, TLR9 stimulation suppressed IFNα, in contrast to increased IFNα from E2-exposed mice. EE and E2 regulated common and hormone-specific expression of immune-related genes. Furthermore, EE exposure resulted in more marked alterations in miRNA expression levels than for E2. Only EE was able to reduce global DNA methylation significantly in splenic leukocytes. Taken together, our novel data revealed that EE and E2 exposure confers more similar effects in innate immune system-related cell development and responses, but has more differential regulatory effects in adaptive immune-related cell development and responses.
Neurology
Poster Background Developing effective therapies for glioblastoma (GBM) relies on robust preclinical animal models that enable detailed investigation of tumor biology, discovery of therapeutic targets, and evaluation of new treatment…
Oncology
Poster Background Ultrahigh-Plex Single-cell Spatial Phenotyping has revealed valuable insights into the tumor immune microenvironment (TiME) for biomarker discovery and stratification of clinical responses. Metabolic reprogramming is a key hallmark…
Neurology
Alzheimer’s Research and Therapy | August 26, 2024 Sampani K, Ness S, Tuz-Zahra F, Aytan N, Spurlock EE, Alluri S, Chen X, Siegel NH, Alosco ML, Xia W, Tripodis Y,…
Neurology
Poster The intersection of new therapeutic options for Alzheimer’s disease (AD), the emergence of accurate blood-based tests for AD, and the anticipated health system log jam for confirmatory diagnostic testing…
Neurology
Alzheimer’s & Dementia | August 3, 2024 Verberk IMW, Jutte J, Kingma MY, Vigneswaran S, Gouda MMTEE, van Engelen MP, Alcolea D, Arranz J, Fortea J, Lleó A, Chevalier C,…
Neurology
Journal of Lipid Research | August 2, 2024 Becktel DA, Frye JB, Le EH, Whitman SA, Schnellmann RG, Morrison HW, Doyle KP. J Lipid Res. 2024 https://doi.org/10.1016/j.jlr.2024.100614 Abstract Ischemic stroke…
