Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media

• Published in: The Journal of immunology (1950) Vol. 194; no. 12; pp. 5990 - 5998
• Main Authors: Lee, Ji-Yun, Komatsu, Kensei, Lee, Byung-Cheol, Miyata, Masanori, O'Neill Bohn, Ashley, Xu, Haidong, Yan, Chen, Li, Jian-Dong
• Format: Journal Article
• Language: English
• Published: United States AAI 15.06.2015
• Subjects: Animals; Cell Line; Disease Models, Animal; Dual Specificity Phosphatase 1 - metabolism; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Gene Expression Regulation - drug effects; Humans; Infectious Disease and Host Response; Mice; Mucin 5AC - genetics; Otitis Media - drug therapy; Otitis Media - genetics; Otitis Media - metabolism; Otitis Media - microbiology; Pneumococcal Infections - drug therapy; Pneumococcal Infections - genetics; Pneumococcal Infections - metabolism; Pneumococcal Infections - microbiology; Streptococcus; Streptococcus pneumoniae; Vinca Alkaloids - administration & dosage; Vinca Alkaloids - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401489

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.