ArticleScientific reports2016
The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Genetically predicted alterations in thyroid function are associated with the risk of benign prostatic disease.Frontiers in endocrinology · 2023Pooled it
- Molecular Determinants of Thyroid Cancer Progression: Thyroid Hormone Signaling, the BRAF/MAPK Pathway, and Emerging miRNA Biomarkers.Biomedicines · 2026Review
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Generation of a Mouse Model for the Study of Thyroid Hormones Regulatory Effect on the Immune System.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Research Advancements in the Interplay between T3 and Macrophages.Current medical science · 2024Review
- Predicting Factors of Worse Prognosis in COVID-19: Results from a Cross-sectional Study on 52 Inpatients Admitted to the Internal Medicine Department.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Association between the Systemic Immune-Inflammation Index and Thyroid Function in U.S. Adults.Mediators of inflammation · 2023Article
- The thyroid hormone enhances mouse embryonic fibroblasts reprogramming to pluripotent stem cells: role of the nuclear receptor corepressor 1.Frontiers in endocrinology · 2023Article
- The Impact of Kohlrabi Sprouts on Various Thyroid Parameters in Iodine Deficiency- and Sulfadimethoxine-Induced Hypothyroid Rats.Nutrients · 2022Article
- Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease.The FEBS journal · 2022Review
- Stem Cell-based Therapy Strategy for Hepatic Fibrosis by Targeting Intrahepatic Cells.Stem cell reviews and reports · 2022Review
- Regulation of metabolic and transcriptional responses by the thyroid hormone in cellular models of murine macrophages.Frontiers in immunology · 2022Article
- Thyroid hormones act as modulators of inflammation through their nuclear receptors.Frontiers in endocrinology · 2022Review
- Article
- Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects.Journal of endocrinological investigation · 2021Review
- COVID-19 and the Endocrine System: A Comprehensive Review on the Theme.Journal of clinical medicine · 2021Review
- Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients.Frontiers in endocrinology · 2021Review
- Thyroid Hormone Action on Innate Immunity.Frontiers in endocrinology · 2019Review
- Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections.
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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.