Department of Otorhinolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630 P.R. China.
Department of Otolaryngology Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630 P.R. China.
Int J Mol Med. 2018 Jul;42(1):248-258. doi: 10.3892/ijmm.2018.3577. Epub 2018 Mar 20.
Otitis media is one of the most common bacterial infections in children, contributing to hearing loss. A vital bacterial pathogen leading to otitis media development is the nontypeable Haemophilus influenzae (NTHi). Inflammation response is reported as an important characristic for otitis media. Chemokine CXC receptor 4 (CXCR4) is a 352-amino acid seven-span transmembrane G-protein coupled receptor, essential for inflammatory response. However, the possible molecular mechanism indicating the alteration of CXCR4 modulated by NTHi is poorly known. In the present study, NTHi enhanced CXCR4 expression through phosphorylation of IKKα and p38, which relied on nuclear factor-κB (NF-κB) translocation in vitro as well as in the middle ear of mice in vivo. Previously, quercetin, a natural production mainly isolated from rutin, has shown anti-inflammatory effects. Here, we report that quercetin suppressed NTHi-induced CXCR4 expression levels in vitro and in vivo. Quercetin blocked CXCR4 activation through direct IKKβ phosphorylation inhibition, as well as of p38 MAPK restraining. Hence, identification of quercetin may be a potential therapeutic strategy for treating otitis media induced by NTHi through inflammation suppression.
中耳炎是儿童最常见的细菌感染之一，可导致听力损失。导致中耳炎发展的重要细菌病原体是非定型流感嗜血杆菌（NTHi）。炎症反应被报道为中耳炎的一个重要特征。趋化因子 CXC 受体 4（CXCR4）是一种由 352 个氨基酸组成的七跨膜 G 蛋白偶联受体，对炎症反应至关重要。然而，由 NTHi 调节的 CXCR4 改变的可能分子机制知之甚少。在本研究中，NTHi 通过 IKKα 和 p38 的磷酸化增强了 CXCR4 的表达，这依赖于核因子-κB（NF-κB）在体外以及体内小鼠中耳中的易位。先前，槲皮素，一种主要从芦丁中分离出来的天然产物，表现出抗炎作用。在这里，我们报告说，槲皮素抑制了 NTHi 在体外和体内诱导的 CXCR4 表达水平。槲皮素通过直接抑制 IKKβ 磷酸化以及抑制 p38 MAPK 来阻断 CXCR4 的激活。因此，鉴定槲皮素可能是通过抑制炎症来治疗 NTHi 引起的中耳炎的潜在治疗策略。
