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Regulation of interleukin-6 release by human thyrocytes
A P Weetman1, R Bright-Thomas, M Freeman
1Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital.
Insights
Thyroid cells release interleukin-6 (IL-6), a key immune signaling molecule. This release, influenced by various factors, may contribute to autoimmune thyroid diseases like Graves
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Autoimmune thyroiditis involves immune cell infiltration of the thyroid gland.
- Thyrocytes (thyroid cells) may contribute to this process by secreting immunomodulatory cytokines.
- Interleukin-6 (IL-6) is a cytokine known to play a role in immune responses.
Purpose of the Study:
- To investigate the release of IL-6 by human thyrocytes.
- To determine the factors influencing IL-6 release from thyrocytes.
- To explore the potential role of thyrocyte-derived IL-6 in autoimmune thyroid diseases and thyroid function.
Main Methods:
- Human thyroid cell cultures (n=9) were established.
- Two bioassays were used to detect and quantify IL-6 release.
- Immunoblotting was employed to confirm the bioactivity as IL-6.
- Thyroid cell cultures were treated with gamma-interferon, tumor necrosis factor, and TSH.
- Exogenous recombinant IL-6 was added to thyroid cell cultures to assess its effect on TSH-stimulated cyclic AMP production.
Main Results:
- IL-6 was detected in all basal culture supernatants.
- IL-6 release significantly increased in response to gamma-interferon, tumor necrosis factor, and TSH in a dose-dependent manner.
- Immunoblotting confirmed the presence of IL-6, and contamination of cultures was ruled out.
- Circulating IL-6 levels were not elevated in patients with Graves' hyperthyroidism.
- Exogenous IL-6 inhibited the cyclic AMP response to TSH in thyroid cells.
Conclusions:
- Human thyrocytes release IL-6 under basal conditions and in response to immune and hormonal stimuli.
- Thyrocyte-derived IL-6 may contribute to the intrathyroidal autoimmune response in Graves' disease and Hashimoto's thyroiditis.
- IL-6 may also directly modulate thyroid cell function, independent of its role in immune cell activation.
Abstract:
Autoimmune thyroiditis is characterized by lymphocytic accumulation within the thyroid which may be the result, in part, of immunomodulatory cytokine secretion by thyrocytes. We have tested human thyroid cell cultures (n = 9) for interleukin-6 (IL-6) release using two bioassays. IL-6 was detected in all culture supernatants under basal conditions and was increased by gamma-interferon, tumour necrosis factor and TSH in a dose-dependent manner. The bioactivity was confirmed as IL-6 by immunoblotting experiments and could not be accounted for by contamination of the thyroid cell cultures with fibroblasts, lymphocytes or monocytes. Circulating IL-6 levels were not raised in patients with Graves' hyperthyroidism. Exogenous recombinant IL-6 reduced cyclic AMP production in response to TSH when added to thyroid cell cultures. Since IL-6 plays a major role in B cell differentiation and T cell activation, release of IL-6 by thyrocytes may increase the intrathyroidal autoimmune response in Graves' disease and Hashimoto's thyroditis. Our results also suggest that IL-6 may modulate thyroid cell function.