Calcitriol inhibits bleomycin-induced early pulmonary inflammatory response and epithelial-mesenchymal transition in mice.
Toxicol Lett
; 240(1): 161-71, 2016 Jan 05.
Article
en En
| MEDLINE
| ID: mdl-26520185
ABSTRACT
Early pulmonary inflammation and epithelial-mesenchymal transition (EMT) play important roles during lung fibrosis. Increasing evidence demonstrates that calcitriol, the active form of vitamin D3, has anti-inflammatory activities. The aim of this study was to investigate the effects of calcitriol on bleomycin (BLM)-induced early pulmonary inflammation and subsequent EMT. Mice were intratracheally injected with BLM (3.0mg/kg). In three calcitriol+BLM groups, mice were intraperitoneal (i.p.) injected with different doses of calcitriol (0.2, 1.0 or 5.0 µg/kg) daily, beginning at 48 h before BLM injection. Twenty-four hours, seven and fourteen days after BLM injection, pulmonary inflammation and EMT were evaluated. As expected, BLM-induced infiltration of inflammatory cells in the lungs was attenuated by calcitriol. BLM-induced pulmonary inflammatory cytokines were repressed by calcitriol. Moreover, BLM-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 was blocked by calcitriol. In addition, BLM-induced phosphorylation of pulmonary p38 MAPK and protein kinase B (Akt) was inhibited by calcitriol. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT in the lungs, was significantly attenuated by calcitriol. BLM-induced transforming growth factor-beta 1 (TGF-ß1) up-regulation and Smad phosphorylation were attenuated by calcitriol. In conclusion, calcitriol inhibits BLM-induced early pulmonary inflammation and subsequent EMT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Bleomicina
/
Calcitriol
/
Transición Epitelial-Mesenquimal
Límite:
Animals
Idioma:
En
Revista:
Toxicol Lett
Año:
2016
Tipo del documento:
Article
País de afiliación:
China