title: A unique combination of inflammatory cytokines enhances apoptosis of thyroid follicular cells and transforms nondestructive to destructive thyroiditis in experimental autoimmune thyroiditis.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Medical Science Research Building III, Ann Arbor, MI 48109, USA.
authors.forename: Su He
authors.initials: SH
authors.lastname: Wang
authors.forename: James D
authors.initials: JD
authors.lastname: Bretz
authors.forename: Ellen
authors.initials: E
authors.lastname: Phelps
authors.forename: Emese
authors.initials: E
authors.lastname: Mezosi
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Arscott
authors.forename: Saho
authors.initials: S
authors.lastname: Utsugi
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: 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*
chemical_list: D001323:Autoantibodies; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013954:Thyroglobulin