ArticlePloS one2012
Estrogen modulates NFκB signaling by enhancing IκBα levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-β.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Effects of exercise intensity and volume on systemic inflammation in overweight and obese postmenopausal women: a dose-response meta-analysis.Frontiers in immunology · 2026Pooled it
- Transdermal 17β-Estradiol for the Treatment of COVID-19: Protocol of an Early Terminated Phase 2 Randomized Controlled Trial.JMIR research protocols · 2026Article
- Nicotine self-administration suppresses both pro- and anti-inflammatory accumbens cytokines but does not induce apoptosis in female rats.Addiction neuroscience · 2026Article
- Estrogen-mediated NF-κB blockade enables breast cancer sensitivity to oncolytic VSV virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Single cell landscape of sex differences in the different courses of multiple sclerosis.Biology of sex differences · 2026Article
- Endothelial Estrogen Receptor Alpha Inhibits Plaque Inflammation in Both Sexes.Circulation research · 2026Article
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- Sex-dependent differences in the progression of renal injury and fibrosis following ischemic acute kidney injury.Clinical science (London, England : 1979) · 2026Article
- Oral contraceptives and tissue factor expression. Comments on "Do combined oral contraceptives induce formation of tissue factor?"Research and practice in thrombosis and haemostasis · 2026Article
- Exploratory analysis of the impact of sex on sputum proteomic response to inhaled wood smoke in humans.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Sex hormones and their receptors in osteoarthritis: current research progress.Annals of joint · 2026Review
- Macrophage polarization regulates bone homeostasis: a potential etiology and therapy for postmenopausal osteoporosis.Frontiers in immunology · 2026Review
- Adaptive immune cells and kidney function in older adults: sex-specific associations in the health and retirement study (HRS).Frontiers in aging · 2026Article
- Uterine inflammation and lessons from large animal models of endometritis.Nature reviews. Immunology · 2025Review
- Combined effects of calorie restriction and chronic stress on systemic inflammation and gut microbiota in rats exposed toBrain, behavior, & immunity - health · 2025Article
- Cognitive Resilience in Apolipoprotein ε4 Carrier Women Predicted by Neuron-Derived Extracellular Vesicles.Annals of clinical and translational neurology · 2025Article
- Effect of Estrogen on Sirt1 Signaling in Human Macrophages.International journal of molecular sciences · 2025Article
- Estradiol Prevents Amyloid Beta-Induced Mitochondrial Dysfunction and Neurotoxicity in Alzheimer's Disease via AMPK-Dependent Suppression of NF-κB Signaling.International journal of molecular sciences · 2025Article
- Sex differences in the association between long-term ambient particulate air pollution and the intestinal microbiome composition of children.Environment international · 2025Article
- Estrogen hindrance escalates inflammation and neurodegeneration in the hippocampal regions of collagen-induced arthritis female Sprague-Dawley rats.Pflugers Archiv : European journal of physiology · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundNFκB signaling is critical for expression of genes involved in the vascular injury response. We have shown that estrogen (17β-estradiol, E2) inhibits expression of these genes in an estrogen receptor (ER)-dependent manner in injured rat carotid arteries and in tumor necrosis factor (TNF)-α treated rat aortic smooth muscle cells (RASMCs). This study tested whether E2 inhibits NFκB signaling in RASMCs and defined the mechanisms. METHODOLOGY/PRINCIPAL
findingsTNF-α treated RASMCs demonstrated rapid degradation of IκBα (10-30 min), followed by dramatic increases in IκBα mRNA and protein synthesis (40-60 min). E2 enhanced TNF-α induced IκBα synthesis without affecting IκBα degradation. Chromatin immunoprecipitation (ChIP) assays revealed that E2 pretreatment both enhanced TNF-α induced binding of NFκB p65 to the IκBα promoter and suppressed TNF-α induced binding of NFκB p65 to and reduced the levels of acetylated histone 3 at promoters of monocyte chemotactic protein (MCP)-1 and cytokine-induced neutrophil chemoattractant (CINC)-2β genes. ChIP analyses also demonstrated that ERβ can be recruited to the promoters of MCP-1 and CINC-2β during co-treatment with TNF-α and E2.
conclusionsThese data demonstrate that E2 inhibits inflammation in RASMCs by two distinct mechanisms: promoting new synthesis of IκBα, thus accelerating a negative feedback loop in NFκB signaling, and directly inhibiting binding of NFκB to the promoters of inflammatory genes. This first demonstration of multifaceted modulation of NFκB signaling by E2 may represent a novel mechanism by which E2 protects the vasculature against inflammatory injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.