Carbocisteine inhibits the expression of Muc5b in COPD mouse model.
Drug Des Devel Ther
; 13: 3259-3268, 2019.
Article
en En
| MEDLINE
| ID: mdl-31571828
ABSTRACT
BACKGROUND:
Cigarette smoke (CS) results in chronic mucus hypersecretion and airway inflammation, contributing to COPD pathogenesis. Mucin 5B (MUC5B) and mucin 5 AC (MUC5AC) are major mucins implicated in COPD pathogenesis. Carbocisteine can reduce mucus viscosity and elasticity. Although carbocisteine decreased human elastase-induced MUC5AC expression in vitro and reduced MUC5AC expression that alleviated bacteria adhesion and improved mucus clearance in vivo, the roles of carbocisteine in inducing MUC5B expression in COPD remain unclear.METHODS:
To investigate the Muc5b/Muc5ac ratio and the gene and protein levels of Muc5b in COPD and carbocisteine intervention models. C57B6J mice were used to develop COPD model by instilling intratracheally with lipopolysaccharide on days 1 and 14 and were exposed to CS for 2 hr twice a day for 12 weeks. Low and high doses of carbocisteine 112.5 and 225 mg/kg/d, respectively, given by gavage administration were applied for the treatment in COPD models for the same duration, and carboxymethylcellulose was used as control. Carbocisteine significantly attenuated inflammation in bronchoalveolar lavage fluid and pulmonary tissue, improved pulmonary function and protected against emphysema.RESULTS:
High-dose carbocisteine significantly decreased the overproduction of Muc5b (P<0.01) and Muc5ac (P<0.001), and restored Muc5b/Muc5ac ratio in COPD model group (P<0.001). Moreover, the Muc5b/Muc5ac ratio negatively correlated with pro-inflammatory cytokines such as IL-6 and keratinocyte-derived cytokine, mean linear intercept, functional residual capacity and airway resistance, but positively correlated with dynamic compliance.CONCLUSIONS:
These findings suggest that carbocisteine attenuated Muc5b and Muc5ac secretion and restored Muc5b protein levels, which may improve mucus clearance in COPD.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbocisteína
/
Enfermedad Pulmonar Obstructiva Crónica
/
Mucina 5B
/
Mucina 5AC
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Drug Des Devel Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2019
Tipo del documento:
Article