Article
Characterization of the Thyroid Hormone System in Rheumatoid Arthritis
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Authors
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Anna-Sophia Pörings
- Innere Medizin 1, Laboratory of Neuroendocrine Immunology and Experimental Rheumatology, Regensburg
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Torsten Lowin
- Innere Medizin I, Laboratory of Neuroendocrine Immunology and Experimental Rheumatology, Regensburg
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Luise Rauch
- Innere Medizin I, Laboratory of Neuroendocrine Immunology and Experimental Rheumatology, Regensburg
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Tanja Späth
- Innere Medizin I, Laboratory of Neuroendocrine Immunology and Experimental Rheumatology, Regensburg
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Angelika Gräber
- Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I, Regensburg
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Rainer H. Straub
- University Hospital Regensburg, Lab. of Exp. Neuroendocrine Immunology and Rheumatology, Dept. of Internal Medicine, Regensburg
| Published: | September 12, 2014 |
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Outline
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Background: Chronic inflammation is characterized by an energy appeal reaction supporting high energy demand of the activated immune system. Thyroid hormones are strongly associated with catabolic effects and are therefore important mediators of energy allocation. Until now, the role of thyroid hormones in the locally inflamed joint is unknown. This study investigates metabolism of thyroid hormones in the joint and demonstrates expression and regulation of thyroid hormone regulating elements in rheumatoid arthritis (RA) and osteoarthritis (OA).
Methods: TSH and thyroid hormones in serum were detected by ELISA. Thyroid hormone receptors TRa, TRb, TA-1, deiodinases DIO1/DIO2/DIO3 and thyroid transporter MOT-8 were stained immunohistochemically in paraffin embedded synovial tissue samples. Influences of cytokines on above mentioned thyroid hormone related proteins were detected by cell-based ELISA. Thyroid receptor-related signaling was analyzed by proteome profiling.
Results: In RA and OA, serum levels of reverse triiodothyronine (rT3), the degradation product of T3, is higher in synovial fluid than in plasma which is opposite for T3 and thyroxine (T4). Serum rT3 relative to free T3 was higher in RA than OA. rT3 levels in superfusate of synovial tissue were higher in RA compared to OA. Staining of synovial tissue revealed expression of thyroid converting enzymes DIO1-3, transporter MOT-8 and nuclear receptors TRa and TRb. Furthermore high expression of TA-1, a receptor for the degradation product of T3, iodothyronamine, was detected. In addition, synovial fibroblast MAP kinase signaling and IL-6 production was altered by thyroid hormones.
Conclusion: Our data demonstrated that thyroid hormones are metabolized locally in the inflamed joint. This local inactivation is more pronounced in RA than OA (higher rT3 levels). Since cytokines might alter the expression of DIO convertases and thyroid receptors, the thyroid hormone system might become dysregulated in the joint during chronic inflammation.
