{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T16:40:48Z","timestamp":1779900048620,"version":"3.53.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Otitis media (OM) is the most common bacterial infection in children. It remains a major health problem and a substantial socioeconomic burden. Streptococcus pneumoniae (S. pneumoniae) is one of the most common bacterial pathogens causing OM. Innate inflammatory response plays a critical role in host defense against bacterial pathogens. However, if excessive, it has a detrimental impact on the middle ear, leading to middle ear inflammation, a hallmark of OM. Currently, there has been limited success in developing effective therapeutic agents to suppress inflammation without serious side effects. In this study, we show that vinpocetine, an antistroke drug, suppressed S. pneumoniae\u2013induced inflammatory response in cultured middle ear epithelial cells as well as in the middle ear of mice. Interestingly, vinpocetine inhibited S. pneumoniae\u2013induced inflammation via upregulating a key negative regulator cylindromatosis (CYLD). Moreover, CYLD suppressed S. pneumoniae\u2013induced inflammation via inhibiting the activation of ERK. Importantly, the postinfection administration of vinpocetine markedly inhibited middle ear inflammation induced by S. pneumoniae in a well-established mouse OM model. These studies provide insights into the molecular mechanisms underlying the tight regulation of inflammation via inhibition of ERK by CYLD and identified vinpocetine as a potential therapeutic agent for suppressing the inflammatory response in the pathogenesis of OM via upregulating negative regulator CYLD expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1901299","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T21:54:19Z","timestamp":1578088459000},"page":"933-942","source":"Crossref","is-referenced-by-count":10,"title":["Vinpocetine Suppresses <i>Streptococcus pneumoniae<\/i>\u2013Induced Inflammation via Inhibition of ERK1 by CYLD"],"prefix":"10.1093","volume":"204","author":[{"given":"Kensei","family":"Komatsu","sequence":"first","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University , Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Hwan","family":"Nam","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University , Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-3981","authenticated-orcid":false,"given":"Ji-Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University , Atlanta, GA 30303"},{"name":"College of Pharmacy, Chung-Ang University , Dongjak-gu, Seoul 06974 ,","place":["South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-1478","authenticated-orcid":false,"given":"Go","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University , Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yan","sequence":"additional","affiliation":[{"name":"Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester Medical Center , Rochester, NY 14642"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University , Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,15]]},"reference":[{"key":"2025030417510781000_r1","first-page":"15","article-title":"Update on otitis media - prevention and treatment","volume":"7","author":"Qureishi","year":"2014","journal-title":"Infect. 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