title: Vinpocetine inhibits Streptococcus pneumoniae-induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media.
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.
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Kensei
authors.initials: K
authors.lastname: Komatsu
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Byung-Cheol
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyata
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Ashley
authors.initials: A
authors.lastname: O'Neill Bohn
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and.
authors.forename: Haidong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642 jdli@gsu.edu Chen_Yan@URMC.Rochester.edu.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; and jdli@gsu.edu Chen_Yan@URMC.Rochester.edu.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D055271:Mucin 5AC / Q000235:genetics*; D010033:Otitis Media / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology; D013296:Streptococcus pneumoniae; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D014748:Vinca Alkaloids; C013983:vinpocetine; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1