Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303.
College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul 06974, South Korea; and.
J Immunol. 2020 Feb 15;204(4):933-942. doi: 10.4049/jimmunol.1901299. Epub 2020 Jan 3.
Otitis media (OM) is the most common bacterial infection in children. It remains a major health problem and a substantial socioeconomic burden. () 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 -induced inflammatory response in cultured middle ear epithelial cells as well as in the middle ear of mice. Interestingly, vinpocetine inhibited -induced inflammation via upregulating a key negative regulator cylindromatosis (CYLD). Moreover, CYLD suppressed -induced inflammation via inhibiting the activation of ERK. Importantly, the postinfection administration of vinpocetine markedly inhibited middle ear inflammation induced by 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.
中耳炎（OM）是儿童最常见的细菌感染。它仍然是一个主要的健康问题，也是一个巨大的社会经济负担。（）是引起 OM 的最常见的细菌病原体之一。先天炎症反应在宿主防御细菌病原体方面起着至关重要的作用。然而，如果过度，它会对中耳造成不利影响，导致中耳炎症，这是 OM 的标志。目前，在开发抑制炎症而没有严重副作用的有效治疗药物方面取得的成功有限。在这项研究中，我们表明长春西汀，一种抗中风药物，抑制了培养的中耳上皮细胞和小鼠中耳中的诱导的炎症反应。有趣的是，长春西汀通过上调关键的负调节剂圆柱瘤（CYLD）抑制了诱导的炎症。此外，CYLD 通过抑制 ERK 的激活抑制了诱导的炎症。重要的是，长春西汀在感染后给药可显著抑制已建立的小鼠 OM 模型中由引起的中耳炎症。这些研究提供了对分子机制的深入了解，即通过 CYLD 抑制 ERK 来严格调节炎症，并确定长春西汀作为一种潜在的治疗药物，通过上调负调节剂 CYLD 的表达来抑制 OM 发病机制中的炎症反应。
