Apoptosis induced by FasL and TRAIL/Apo2L in the pathogenesis of thyroid diseases

• Published in: Trends in Endocrinology & Metabolism 2001-11, Vol.12 (9), p.384-390
• Main Authors: Mitsiades, Nicholas, Poulaki, Vassiliki, Mitsiades, Constantine S, Koutras, Demetrios A, Chrousos, George P
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - physiology; Apoptosis Regulatory Proteins; Fas; Fas Ligand Protein; fas Receptor - metabolism; FasL; Graves Disease - metabolism; Humans; Membrane Glycoproteins - physiology; Thyroid; Thyroid Diseases - etiology; Thyroid Neoplasms - physiopathology; TNF-Related Apoptosis-Inducing Ligand; TRAIL/Apo21; Tumor Necrosis Factor-alpha - physiology
• ISSN: 1043-2760; 1879-3061
• DOI: 10.1016/S1043-2760(01)00441-6

FasL and TRAIL/Apo2L participate in cell-mediated cytotoxicity by inducing apoptosis in susceptible cells via respective cell surface receptors. Normal and neoplastic thyroid tissues are resistant to FasL-induced apoptosis but are sensitized by Th-1-type cytokines. In Hashimoto's thyroiditis, both FasL and its receptor, Fas, are strongly upregulated and their interaction leads to the suicidal/fratricidal death of thyrocytes. In Graves’ disease, FasL expression in thyroid follicular cells is induced by thionamides and kills infiltrating lymphocytes. In this condition, Th-2-type cytokines upregulate the anti-apoptotic molecules FLIP and Bcl-x L and protect thyrocytes from apoptosis. FasL is expressed by neoplastic thyrocytes and induces apoptosis of infiltrating lymphocytes. TRAIL/Apo2L kills thyroid carcinoma cells but spares normal thyrocytes, thus providing a potential therapy for thyroid cancer. The regulation of apoptosis plays a key role in health and disease. Novel findings about apoptosis in the thyroid offer insight into the pathophysiology of thyroid diseases and put us on the TRAIL for the cure of thyroid cancer.