title: Apoptosis induced by FasL and TRAIL/Apo2L in the pathogenesis of thyroid diseases.
abstract: 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.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Mayer Building, Room M557, 44 Binney Street, Boston, MA 02115, USA. mitsiades@netscape.net
authors.forename: N
authors.initials: N
authors.lastname: Mitsiades
authors.forename: V
authors.initials: V
authors.lastname: Poulaki
authors.forename: C S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: D A
authors.initials: DA
authors.lastname: Koutras
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053222:Fas Ligand Protein; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D013959:Thyroid Diseases / Q000209:etiology*; D013964:Thyroid Neoplasms / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
chemical_list: 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