Wnt-4 protects thymic epithelial cells against dexamethasone-induced senescence.
Rejuvenation Res
; 14(3): 241-8, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21453014
ABSTRACT
Glucocorticoids are widely used immunosuppressive drugs in treatment of autoimmune diseases and hematological malignancies. Glucocorticoids are particularly effective immune suppressants, because they induce rapid peripheral T cell and thymocyte apoptosis resulting in impaired T cell-dependent immune responses. Although glucocorticoids can induce apoptotic cell death directly in developing thymocytes, how exogenous glucocorticoids affect the thymic epithelial network that provides the microenvironment for T cell development is still largely unknown. In the present work, we show that primary thymic epithelial cells (TECs) express glucocorticoid receptors and that high-dosage dexamethasone induces degeneration of the thymic epithelium within 24 h of treatment. Changes in organ morphology are accompanied by a decrease in the TEC transcription factor FoxN1 and its regulator Wnt-4 parallel with upregulation of lamina-associated polypeptide 2α and peroxisome proliferator activator receptor γ, two characteristic molecular markers for adipose thymic involution. Overexpression of Wnt-4, however, can prevent upregulation of adipose differentiation-related aging markers, suggesting an important role of Wnt-4 in thymic senescence.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Dexametasona
/
Senescência Celular
/
Citoproteção
/
Células Epiteliais
/
Proteína Wnt4
Limite:
Animals
Idioma:
En
Revista:
Rejuvenation Res
Assunto da revista:
FISIOLOGIA
/
GERIATRIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Hungria