The role of apoptosis in thyroid disease.
Increasing evidence suggests that apoptosis plays an important role in the pathogenesis of autoimmune and proliferative thyroid diseases, and that the apoptotic pathways involved are complex and highly regulated. Autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease have been associated with differential expression of Fas and TRAIL receptor-mediated apoptosis. Thus, the thyroid cell destruction characteristic of autoimmune thyroiditis can be seen as the consequence of inappropriate expression of Fas or TRAIL death pathway molecules and down-regulation of the apoptosis controlling protein Bcl-2, which may be induced by cytokines released locally by infiltrating lymphocytes. In contrast, Graves' thyrocytes are protected from apoptotic death possibly by the anti-apoptotic action of thyrotrophin receptor antibodies or soluble Fas and/or the overexpression of Fas ligand which all create an anti-apoptotic potential for the thyroid cells and favor apoptosis of the infiltrating lymphocytes. On the other hand, an imbalance between thyroid cell proliferation and cell death may be crucial for goiter formation or cancer development and progression. In human thyroid goiter, Fas-mediated apoptosis is suppressed, leading to thyroid cell hyperplasia. Furthermore, malignant thyroid cells may escape immune attack by over expressing Fas ligand and inducing apoptosis in the invading immune cells. However, the exact mechanisms involved in the regulation of apoptosis in thyroid disease remain unclear. Further investigation is needed that may provide new strategies in the prevention and treatment of these diseases.
Tsatsoulis
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Department of Medicine, Division of Endocrinology, University of Ioannina, Ioannina, Greece. atsatsou@cc.uoi.gr
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; D006042:Goiter / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D013964:Thyroid Neoplasms / Q000473:pathology / Q000503:physiopathology; D013967:Thyroiditis, Autoimmune / Q000473:pathology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor