Fas (APO-1, CD95)-mediated apoptosis in thyroid cells is regulated by a labile protein inhibitor.
To determine whether thyroid cell apoptosis observed in autoimmune thyroid disease could be related to activation of the Fas pathway, we examined the expression and function of Fas on thyroid follicular cells in vitro. Fas messenger RNA was found to be present using two different techniques and was expressed at equal levels in thyrocytes cultured either in the presence or absence of TSH. Fas antigen protein expression was demonstrated by Western blot of thyroid cell lysates and by immunohistochemical staining of thyrocytes, and the amount of Fas protein present did not appear to vary regardless of culture conditions. Despite expressing substantial amounts of Fas protein, thyrocytes treated with anti-Fas monoclonal antibody failed to undergo apoptosis. The addition of either interferon-gamma or interleukin-1beta to the anti-Fas-treated cell cultures also did not promote apoptotic signaling through this pathway. In contrast, the concomitant administration of cycloheximide allowed the induction of apoptosis through the activation of Fas in thyrocytes. These results suggest that Fas is constitutively expressed in thyrocytes, but that the induction of apoptosis through the Fas pathway is blocked by a labile protein inhibitor.
Arscott
P L
PL
Department of Medicine, University of Michigan Medical School, Ann Arbor 48109-0666, USA.
Knapp
J
J
Rymaszewski
M
M
Bartron
J L
JL
Bretz
J D
JD
Thompson
N W
NW
Baker
J R
JR
D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019014:fas Receptor; D003513:Cycloheximide