Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice.
Inhal Toxicol
; 23(8): 486-94, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21689010
ABSTRACT
Ozone (O3), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O3-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O3 exposure protocol consisting of 2 days of filtered air and 5 days of O3 exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-ß), the most potent profibrogenic cytokine. The results showed that O3 exposure for 5 or 10 cycles increased the TGF-ß protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-ß-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O3 exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O3 exposure. Importantly, blockage of the TGF-ß signaling pathway with IN-1233 suppressed O3-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O3 exposure increases TGF-ß expression and activates TGF-ß signaling pathways, which mediates O3-induced lung fibrotic responses in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oxidantes Fotoquímicos
/
Ozono
/
Fibrosis Pulmonar
/
Bronquios
/
Factor de Crecimiento Transformador beta1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Inhal Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos