Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media.
J Immunol
; 194(12): 5990-8, 2015 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-25972475
ABSTRACT
Mucin overproduction is a hallmark of otitis media (OM). Streptococcus pneumoniae is one of the most common bacterial pathogens causing OM. Mucin MUC5AC plays an important role in mucociliary clearance of bacterial pathogens. However, if uncontrolled, excessive mucus contributes significantly to conductive hearing loss. Currently, there is a lack of effective therapeutic agents that suppress mucus overproduction. In this study, we show that a currently existing antistroke drug, vinpocetine, a derivative of the alkaloid vincamine, inhibited S. pneumoniae-induced mucin MUC5AC upregulation in cultured middle ear epithelial cells and in the middle ear of mice. Moreover, vinpocetine inhibited MUC5AC upregulation by inhibiting the MAPK ERK pathway in an MKP-1-dependent manner. Importantly, ototopical administration of vinpocetine postinfection inhibited MUC5AC expression and middle ear inflammation induced by S. pneumoniae and reduced hearing loss and pneumococcal loads in a well-established mouse model of OM. Thus, these studies identified vinpocetine as a potential therapeutic agent for inhibiting mucus production in the pathogenesis of OM.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Otite Média
/
Infecções Pneumocócicas
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Alcaloides de Vinca
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Fosfatase 1 de Especificidade Dupla
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Mucina-5AC
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article