Induction and regulation of fas-mediated apoptosis in human thyroid epithelial cells

E. Mezősi, Su He Wang, Saho Utsugi, L. Bajnok, James D. Bretz, Paul G. Gauger, Norman W. Thompson, James R. Baker

Research output: Contribution to journalArticle

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Abstract

Fas-mediated apoptosis has been proposed to play an important role in the pathogenesis of Hashimoto's thyroiditis. Normal thyroid cells are resistant to Fas-mediated apoptosis in vitro but can be sensitized by the unique combination of interferon-γ and IL-1β cytokines. We sought to examine the mechanism of this sensitization and apoptosis signaling in primary human thyroid cells. Without the addition of cytokines, agonist anti-Fas antibody treatment of the thyroid cells resulted in the cleavage of proximal caspases, but this did not lead to the activation of caspase 7 and caspase 3. Apoptosis associated with the cleavage of caspases 7, 3, and Bid, and the activation of mitochondria in response to anti-Fas antibody occurred only after cytokine pretreatment. Cell surface expression of Fas, the cytoplasmic concentrations of procaspases 7, 8, and 10, and the proapoptotic molecule Bid were markedly enhanced by the presence of the cytokines. In contrast, P44/p42 MARK (Erk) appeared to provide protection from Fas-mediated apoptosis because an MAPK kinase inhibitor (U0126) sensitized thyroid cells to anti-Fas antibody. In conclusion, Fas signaling is blocked in normal thyroid cells at a point after the activation of proximal caspases. Interferon-γ/IL-1β pretreatment sensitizes human thyroid cells to Fas-mediated apoptosis in a complex manner that overcomes this blockade through increased expression of cell surface Fas receptor, increases in proapoptotic molecules that result in mitochondrial activation, and late caspase cleavage. This process involves Bcl-2 family proteins and appears to be compatible with type II apoptosis regulation.

Original languageEnglish
Pages (from-to)804-811
Number of pages8
JournalMolecular Endocrinology
Volume19
Issue number3
DOIs
Publication statusPublished - Mar 2005

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Thyroid Gland
Apoptosis
Caspase 7
Caspases
Cytokines
Anti-Idiotypic Antibodies
Interleukin-1
Caspase 3
Interferons
CD95 Antigens
Hashimoto Disease
Caspase 8
Mitogen-Activated Protein Kinase Kinases
Cell Surface Receptors
Thyroid Epithelial Cells
Mitochondria
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Induction and regulation of fas-mediated apoptosis in human thyroid epithelial cells. / Mezősi, E.; Wang, Su He; Utsugi, Saho; Bajnok, L.; Bretz, James D.; Gauger, Paul G.; Thompson, Norman W.; Baker, James R.

In: Molecular Endocrinology, Vol. 19, No. 3, 03.2005, p. 804-811.

Research output: Contribution to journalArticle

Mezősi, E, Wang, SH, Utsugi, S, Bajnok, L, Bretz, JD, Gauger, PG, Thompson, NW & Baker, JR 2005, 'Induction and regulation of fas-mediated apoptosis in human thyroid epithelial cells', Molecular Endocrinology, vol. 19, no. 3, pp. 804-811. https://doi.org/10.1210/me.2004-0286
Mezősi, E. ; Wang, Su He ; Utsugi, Saho ; Bajnok, L. ; Bretz, James D. ; Gauger, Paul G. ; Thompson, Norman W. ; Baker, James R. / Induction and regulation of fas-mediated apoptosis in human thyroid epithelial cells. In: Molecular Endocrinology. 2005 ; Vol. 19, No. 3. pp. 804-811.
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