Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea.
Biochem Biophys Res Commun. 2019 Apr 23;512(1):53-59. doi: 10.1016/j.bbrc.2019.02.146. Epub 2019 Mar 8.
Exposure to diesel exhaust particles (DEPs) is known to cause serious health problems, owing to a steady increase in the number of diesel vehicles worldwide. DEPs comprise approximately 90% particle mass existing in the fine size range (≤2.5 μm) and are mainly absorbed in the respiratory tract. However, limited information is available on the effects of DEP exposure on the respiratory tract in humans. Here, we investigated the effect and signaling pathways of DEPs on the expression of mucin, especially MUC5AC and MUC5B, in human airway epithelial cells by reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence staining. The signaling pathways activated following DEP-induced expression of MUC5AC and MUC5B in airway epithelial cells were analyzed by evaluating Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2 [ERK1/2] and p38), and nuclear factor kappa B (NF-κB) phosphorylation with western blot and small-interfering RNA (siRNA) analyses. DEPs significantly increased MUC5AC and MUC5B expression in human airway epithelial cells that was closely related to TLR4, MAPK (ERK 1/2 and p38), and NF-κB pathway activation. This is the first report to demonstrate the DEP-mediated increase in MUC5AC and MUC5B expression via the TLR4-mediated activation of ERK1/2, p38 MAPK, and NF-κB signaling pathways in human airway epithelial cells.
暴露于柴油废气颗粒（DEP）已知会导致严重的健康问题，这是由于全球柴油车辆数量的稳步增加。DEP 约占存在于细颗粒范围内（≤2.5μm）的颗粒质量的 90%，主要被呼吸道吸收。然而，关于 DEP 暴露对人类呼吸道的影响的信息有限。在这里，我们通过逆转录聚合酶链反应（PCR）、实时 PCR、酶联免疫吸附测定、western blot 和免疫荧光染色，研究了 DEP 对人呼吸道上皮细胞中粘蛋白（特别是 MUC5AC 和 MUC5B）表达的影响和信号通路。通过评估 Toll 样受体 4（TLR4）、丝裂原活化蛋白激酶（MAPK；细胞外信号调节激酶 1/2 [ERK1/2] 和 p38）和核因子 kappa B（NF-κB）磷酸化，分析了 DEP 诱导气道上皮细胞中 MUC5AC 和 MUC5B 表达后激活的信号通路，并用 western blot 和小干扰 RNA（siRNA）分析进行分析。DEP 显著增加了人呼吸道上皮细胞中 MUC5AC 和 MUC5B 的表达，这与 TLR4、MAPK（ERK1/2 和 p38）和 NF-κB 途径的激活密切相关。这是首次报道表明，DEP 通过 TLR4 介导的 ERK1/2、p38 MAPK 和 NF-κB 信号通路的激活，介导 MUC5AC 和 MUC5B 的表达增加。
