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A critical role for TRAIL in resolution of granulomatous experimental autoimmune thyroiditis.
Fang, Y; Sharp, G C; Yagita, H; Braley-Mullen, H.
Afiliação
  • Fang Y; Research Service, Harry S Truman Memorial VA Hospital, University of Missouri, Columbia, MO 65212, USA. fangy@health.missouri.edu
J Pathol ; 216(4): 505-13, 2008 Dec.
Article em En | MEDLINE | ID: mdl-18810759
ABSTRACT
Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin (MTG)-sensitized splenocytes activated in vitro with MTG and IL-12. Thyroid lesions reach maximal severity 20 days after cell transfer, and usually resolve or progress to fibrosis by day 60 depending on the extent of thyroid damage at day 20. Our previous studies indicated that neutralization of TNF-alpha or FasL had no effect on G-EAT induction, but neutralization of TNF-alpha promoted, while neutralization of FasL inhibited, G-EAT resolution. TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. This study was undertaken to define the role of endogenous TRAIL in G-EAT development and/or resolution. Neutralization of endogenous TRAIL had little effect on G-EAT induction, but significantly inhibited G-EAT resolution and increased thyroid fibrosis. This correlated with higher expression of pro-inflammatory cytokines and preferential expression of the pro-apoptotic molecule TRAIL, and anti-apoptotic molecules FLIP and Bcl-xL on inflammatory cells in thyroids of anti-TRAIL-treated recipients. The results suggest that endogenous TRAIL is not required for G-EAT development in recipients, but is critical for G-EAT resolution. Endogenous TRAIL might promote resolution, at least in part, through modulation of the balance between pro- and anti-inflammatory cytokines, and the expression pattern of pro- and anti-apoptotic molecules of thyroid epithelial cells (TECs) and inflammatory cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Tireoidite Subaguda / Tireoidite Autoimune / Ligante Indutor de Apoptose Relacionado a TNF Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Pathol Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Tireoidite Subaguda / Tireoidite Autoimune / Ligante Indutor de Apoptose Relacionado a TNF Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Pathol Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Estados Unidos