Abstract：
Chronic obstructive pulmonary disease (COPD) induces serious social and economic burdens due to its high disability and mortality, the pathogenesis of which is highly involved with inflammation, oxidative stress (OS), and mechanism of mucin 5AC (MUC5AC) secretion. Lixisenatide is a selective glucagon-like peptide 1 receptor agonist recently reported to have anti-inflammatory properties. Our study will focus on the potential impact of lixisenatide on lipopolysaccharide (LPS)-induced mucin secretion and inflammation in 16 human bronchial epithelial (16HBE) cells to check its potential function in COPD. 16HBE cells were treated with LPS, with or without lixisenatide (10 and 20 nM) for 1 day. Remarkably declined cell viability, enhanced lactate dehydrogenase release, activated OS, and elevated release of inflammatory cytokines were observed in LPS-treated 16HBE cells, accompanied by the activation of nuclear factor-κB signaling, all of which were signally reversed by lixisenatide. Moreover, elevated expression and release of MUC5AC were observed in LPS-treated 16HBE cells but were markedly repressed by lixisenatide. Furthermore, the repressed nuclear factor erythroid 2-related factor 2 (Nrf2) level in LPS-treated 16HBE cells was notably rescued by lixisenatide. Lastly, following the knockdown of Nrf2, the protective function of lixisenatide on LPS-triggered MUC5AC release in 16HBE cells was significantly abrogated. Collectively, lixisenatide ameliorated LPS-induced expression of mucin and inflammation in bronchial epithelial cells by regulating Nrf2.
摘要：
慢性阻塞性肺疾病(COPD)因其高致残率和高死亡率而引起严重的社会经济负担,其发病机制与炎症高度相关，氧化应激（OS），和粘蛋白5AC（MUC5AC）分泌机制。Lixisenadide是一种选择性的胰高血糖素样肽1受体激动剂，最近报道具有抗炎特性。我们的研究将集中在利西拉来对脂多糖（LPS）诱导的16人支气管上皮细胞（16HBE）的粘蛋白分泌和炎症的潜在影响，以检查其在COPD中的潜在功能。用LPS处理16HBE细胞，有或没有利西拉来(10和20nM)持续1天。细胞活力显著下降，增强乳酸脱氢酶释放，激活的操作系统，在LPS处理的16HBE细胞中观察到炎症细胞因子的释放升高，伴随着核因子-κB信号的激活，所有这些都被利西拉来明显逆转。此外，在LPS处理的16HBE细胞中观察到MUC5AC的表达和释放升高,但利西拉来显著抑制了MUC5AC的表达和释放.此外，利西拉来显著挽救了LPS处理的16HBE细胞中抑制的核因子-类红细胞2相关因子2(Nrf2)水平.最后,Nrf2敲低后，利西拉来对LPS触发的MUC5AC在16HBE细胞中的保护功能被显著取消。总的来说，利西拉来通过调节Nrf2改善LPS诱导的支气管上皮细胞粘蛋白表达和炎症。
