ArticleProceedings of the National Academy of Sciences of the United States of America2012
2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory Markers of HIV-Infected Women.Journal of acquired immune deficiency syndromes (1999) · 2016Trial
- Abatement of acrylonitrile-induced gastric injury by 2-Methoxyestradiol through inhibition of TLR4/MYD88/phospho-p38 MAPK axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- Inhibition of STAT3 by 2-Methoxyestradiol suppresses M2 polarization and protumoral functions of macrophages in breast cancer.BMC cancer · 2024Article
- Protective Effects of 2-Methoxyestradiol on Acute Isoproterenol-Induced Cardiac Injury in Rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- HIF-1α participates in secondary brain injury through regulating neuroinflammation.Translational neuroscience · 2023Article
- Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.Frontiers in immunology · 2023Article
- 2-Difluoromethoxy-Substituted Estratriene Sulfamates: Synthesis, Antiproliferative SAR, Antitubulin Activity, and Steroid Sulfatase Inhibition.ChemMedChem · 2022Article
- Restricted Activation of the NF-κB Pathway in Individuals with Latent Tuberculosis Infection after HIF-1α Blockade.Biomedicines · 2022Article
- Is Estrogen a Missing Culprit in Thyroid Eye Disease? Sex Steroid Hormone Homeostasis Is Key to Other Fibrogenic Autoimmune Diseases - Why Not This One?Frontiers in immunology · 2022Article
- 2-Methoxyestradiol Alleviates Neuroinflammation and Brain Edema in Early Brain Injury After Subarachnoid Hemorrhage in Rats.Frontiers in cellular neuroscience · 2022Article
- 2-Methoxyestradiol Ameliorates Angiotensin II-Induced Hypertension by Inhibiting Cytosolic Phospholipase AHypertension (Dallas, Tex. : 1979) · 2021Article
- 2-Methoxyestradiol and its derivatives inhibit store-operated CaBiochimica et biophysica acta. Molecular cell research · 2021Article
- 2-Methoxyestradiol Protects Against Lung Ischemia/Reperfusion Injury by Upregulating Annexin A1 Protein Expression.Frontiers in immunology · 2021Article
- Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2019Review
- Novel combination of 2-methoxyestradiol and cyclophosphamide enhances the antineoplastic and pro-apoptotic effects on S-180 ascitic tumour cells.Journal of cell communication and signaling · 2018Article
- Sex Hormones in Acquired Immunity and Autoimmune Disease.Frontiers in immunology · 2018Review
- Neuroprotective effects of estrogen in CNS injuries: insights from animal models.Neuroscience and neuroeconomics · 2017Article
- 2-Methoxyestradiol, an endogenous 17β-estradiol metabolite, inhibits microglial proliferation and activation via an estrogen receptor-independent mechanism.American journal of physiology. Endocrinology and metabolism · 2016Article
- 2-Methoxyestradiol Alleviates Experimental Autoimmune Uveitis by Inhibiting Lymphocytes Proliferation and T Cell Differentiation.BioMed research international · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-κB and activator protein 1 (AP-1) activation were not adversely affected. We therefore propose that 2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.
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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.