ArticleThyroid : official journal of the American Thyroid Association2010
A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves' orbital preadipocyte fibroblasts.
Article in Thyroid : official journal of the American Thyroid Association, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 72 citations in OpenAlex.
- The role of monoclonal antibodies against IL-6 or IL-6R in the treatment of thyroid eye disease.Reviews in endocrine & metabolic disorders · 2026Review
- What has changed in thyroid eye disease in the last five years (2020-2025).European thyroid journal · 2026Review
- The therapeutic revolution in thyroid eye disease: from orbital radiotherapy to teprotumumab and AI.Frontiers in medicine · 2026Review
- Article
- Targeted Delivery of CD34 Aptamer-Coupled Tocilizumab Microspheres for Effective Treatment of Thyroid-Associated Ophthalmopathy.Investigative ophthalmology & visual science · 2025Article
- Targeted immunotherapies for Graves' thyroidal & orbital diseases.Frontiers in immunology · 2025Review
- The TSH Receptor Antibody Reactome Contributes to Retro-Orbital Inflammation.Journal of the Endocrine Society · 2024Article
- Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells.International journal of molecular sciences · 2023Article
- A review of TSHR- and IGF-1R-related pathogenesis and treatment of Graves' orbitopathy.Frontiers in immunology · 2023Review
- Current concepts regarding Graves' orbitopathy.Journal of internal medicine · 2022Review
- Teprotumumab Divergently Alters Fibrocyte Gene Expression: Implications for Thyroid-associated Ophthalmopathy.The Journal of clinical endocrinology and metabolism · 2022Article
- Mechanisms in Graves Eye Disease: Apoptosis as the End Point of Insulin-Like Growth Factor 1 Receptor Inhibition.Thyroid : official journal of the American Thyroid Association · 2022Article
- The risk factors for Graves' ophthalmopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Review
- RhoA with Associated TRAb or FT3 in the Diagnosis and Prediction of Graves' Ophthalmopathy.Disease markers · 2022Article
- Steroid-Resistant Graves' Orbitopathy Treated with Tocilizumab in Real-World Clinical Practice: A 9-Year Single-Center Experience.Journal of clinical medicine · 2021Article
- Novel Approaches for Immunosuppression in Graves' Hyperthyroidism and Associated Orbitopathy.European thyroid journal · 2020Article
- Therapeutic Effect of Guggulsterone in Primary Cultured Orbital Fibroblasts Obtained From Patients with Graves' Orbitopathy.Investigative ophthalmology & visual science · 2020Article
- Thyroid-associated ophthalmopathy: Emergence of teprotumumab as a promising medical therapy.Best practice & research. Clinical endocrinology & metabolism · 2020Review
- Insulin-like Growth Factor-I Receptor and Thyroid-Associated Ophthalmopathy.Endocrine reviews · 2019Review
- Editorial: TSH Receptor and Autoimmunity.Frontiers in endocrinology · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPatients with Graves' ophthalmopathy (GO) have circulating autoantibodies directed against the thyrotropin receptor (TSHR) and elevated levels of the proinflammatory cytokine interleukin-6 (IL-6) in both serum and orbital tissues. We hypothesized that these autoantibodies might increase IL-6 expression and secretion in preadipocyte fibroblasts and adipocytes from patients with GO, and thus directly impact the clinical activity of the disease.
methodsIL-6 mRNA levels were measured in cultures of GO orbital preadipocytes (n = 3) treated during adipocyte differentiation with a monoclonal stimulatory TSHR antibody (M22; 10 ng/mL), IL-6 (1 ng/mL), or TSH (10 U/L). Additionally, levels of IL-6 protein secretion were assessed after adipocyte differentiation in orbital cultures exposed to TSH or M22 for 24 or 48 hours (n = 8). IL-6 mRNA levels were also measured in orbital adipose tissue specimens from well-characterized GO patients (n = 9) and normal individuals (n = 9).
resultsTreatment of GO orbital preadipocyte cultures with IL-6, TSH, or M22 during adipocyte differentiation resulted in increased IL-6 mRNA levels (3.1-fold, 2.9-fold, and 2.7-fold, respectively; p < 0.05). Treatment of orbital cultures with M22 or TSH after adipocyte differentiation enhanced the release of IL-6 protein into the medium at both 24 and 48 hours for TSH (mean 1.9- and 2.3-fold; p = 0.002 and 0.015, respectively) and at 48 hours for M22 (mean 2.0-fold; p = 0.005). In addition, we found mean IL-6 mRNA levels to be significantly increased in GO orbital adipose tissue specimens (10-fold; p < 0.01), primarily attributable to high levels in three of the four patients with clinical activity scores >or=5.
conclusionsBoth TSH and M22 increase IL-6 expression in orbital preadipocyte fibroblasts and IL-6 secretion by mature adipocytes. These results suggest that circulating TSHR autoantibodies in GO might play a direct role in the clinical activity of the disease.
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