A unique combination of inflammatory cytokines enhances apoptosis of thyroid follicular cells and transforms nondestructive to destructive thyroiditis in experimental autoimmune thyroiditis.
Treatment of cultured primary human thyroid cells with IFN-gamma and TNF-alpha uniquely allows the induction of Fas-mediated apoptosis. To investigate the role of this cytokine combination in vivo, CBA/J mice were immunized with thyroglobulin and then injected with IFN-gamma and TNF-alpha. Compared with control animals, mice treated with IFN-gamma and TNF-alpha showed significantly sustained lymphocytic infiltration in the thyroid, which was associated with the destruction of portions of the follicular architecture at wk 6 after initial immunization. Furthermore, the number of apoptotic thyroid follicular cells was increased only in the thyroids from mice treated with the IFN-gamma and TNF-alpha. We also analyzed the function of the Fas pathway in vivo in cytokine-treated mice by using an agonist anti-Fas Ab injected directly into the thyroid. Minimal apoptosis of thyroid epithelial cells was observed unless the mice were pretreated with IFN-gamma and TNF-alpha. These data demonstrate that this unique combination of inflammatory cytokines facilitates the apoptotic destruction of thyroid follicular cells in experimental autoimmune thyroiditis, in a manner similar to what is observed in Hashimoto's thyroiditis in humans.
Wang
Su He
SH
Department of Internal Medicine, University of Michigan Medical Center, Medical Science Research Building III, Ann Arbor, MI 48109, USA.
Bretz
James D
JD
Phelps
Ellen
E
Mezosi
Emese
E
Arscott
Patricia L
PL
Utsugi
Saho
S
Baker
James R
JR
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000473:pathology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013954:Thyroglobulin