Bone morphogenetic protein 6 (BMP-6) modulates lung function, pulmonary iron levels and cigarette smoke-induced inflammation.
Mucosal Immunol
; 12(2): 340-351, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-30542109
ABSTRACT
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and airway wall remodeling, leading to reduced lung function. An association between the bone morphogenetic protein (BMP-6) locus and forced vital capacity has been found in a genome-wide association study. However, the role of BMP-6 in the pathogenesis of COPD remains unknown. The pulmonary expression of BMP-6 was analyzed in patients with COPD and in cigarette smoke (CS)-exposed mice. We evaluated lung function and histology in BMP-6 KO mice at baseline. We exposed BMP-6 KO mice to CS for 4 weeks and measured pulmonary inflammation and iron levels. Pulmonary mRNA levels of BMP-6 were decreased in smokers with and without COPD and in CS-exposed mice. Importantly, BMP-6 expression was lowest in severe COPD. Accordingly, protein levels of BMP-6 were decreased in patients with COPD. Lung function measurements demonstrated a decreased compliance and total lung capacity in BMP-6 KO mice, whereas lung histology was normal. Furthermore, BMP-6 KO mice displayed elevated iron levels and an aggravated CS-induced inflammatory response. These results suggest that BMP-6 is important for normal lung function and that downregulation of BMP-6-as observed in patients with COPD-contributes to pulmonary inflammation after CS exposure.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neumonía
/
Enfermedad Pulmonar Obstructiva Crónica
/
Proteína Morfogenética Ósea 6
/
Hierro
/
Pulmón
Tipo de estudio:
Etiology_studies
Límite:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Mucosal Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Bélgica