Compartmentalized expression of c-FLIP in lung tissues of patients with idiopathic pulmonary fibrosis.
Am J Respir Cell Mol Biol
; 42(2): 140-8, 2010 Feb.
Article
en En
| MEDLINE
| ID: mdl-19372246
ABSTRACT
Increased apoptosis of alveolar epithelial cells and impaired apoptosis of myofibroblasts have been linked to the pathogenesis of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). Fas, a death receptor of the TNF-receptor superfamily, has been implicated in apoptosis of both cell types, though the mechanisms are poorly understood. The goals of this study were (1) to examine the localization of Fas-associated death-domain-like IL-1beta-converting enzyme inhibitory protein (c-FLIP), an NF-kappaB-dependent regulator of Fas-signaling, in lung tissues from IPF/UIP patients and control subjects; and (2) to compare c-FLIP expression with epithelial cell and myofibroblast apoptosis, proliferation, and NF-kappaB activation. c-FLIP expression was restricted to airway epithelial cells in control lung tissues. In contrast, in patients with IPF/UIP, c-FLIP was also expressed by alveolar epithelial cells in areas of injury and fibrosis, but was absent from myofibroblasts in fibroblastic foci and from alveolar epithelial cells in uninvolved areas of lung tissue. Quantification of apoptosis and proliferation revealed an absence of apoptotic or proliferating cells in fibroblastic foci and low levels of apoptosis and proliferation by alveolar epithelial cells. Quantification of NF-kappaB expression and nuclear translocation revealed strong staining and translocation in alveolar epithelial cells and weak staining and minimal nuclear translocation in myofibroblasts. These findings suggest that (1) c-FLIP expression is induced in the abnormal alveolar epithelium of patients with IPF/UIP, (2) the resistance of myofibroblasts to apoptosis in patients with IPF/UIP occurs independently of c-FLIP expression, and (3) increased NF-kappaB activation and c-FLIP expression by the alveolar epithelium may be linked.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Reguladora de Apoptosis Similar a CASP8 y FADD
/
Fibrosis Pulmonar Idiopática
/
Pulmón
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos