Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis.
The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood. Thyrocytes from HT glands, but not from nonautoimmune thyroids, expressed Fas. Interleukin-1beta (IL-1beta), abundantly produced in HT glands, induced Fas expression in normal thyrocytes, and cross-linking of Fas resulted in massive thyrocyte apoptosis. The ligand for Fas (FasL) was shown to be constitutively expressed both in normal and HT thyrocytes and was able to kill Fas-sensitive targets. Exposure to IL-1beta induced thyrocyte apoptosis, which was prevented by antibodies that block Fas, suggesting that IL-1beta-induced Fas expression serves as a limiting factor for thyrocyte destruction. Thus, Fas-FasL interactions among HT thyrocytes may contribute to clinical hypothyroidism.
Giordano
C
C
Laboratory of Immunology, Endocrinology Section, Institute of Clinica Medica, University of Palermo, Palermo, Italy.
Stassi
G
G
De Maria
R
R
Todaro
M
M
Richiusa
P
P
Papoff
G
G
Ruberti
G
G
Bagnasco
M
M
Testi
R
R
Galluzzo
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019014:fas Receptor