Choi Yoon Seok, Bae Chang Hoon, Song Si-Youn, Kim Yong-Dae
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Am J Rhinol Allergy. 2015 May-Jun;29(3):161-5. doi: 10.2500/ajra.2015.29.4162.
Asian sand dust (ASD) is a natural phenomenon and originates from the deserts of China and is known to contain various chemical and biomolecular components that enhance airway inflammation. The overproduction of airway mucins is an important pathologic finding in inflammatory airway diseases. However, the mechanism of ASD on mucin production of airway epithelial cells has not been elucidated.
To investigate the effect and signaling pathway of ASD on mucin expressions in human airway epithelial cells.
In the NCI-H292 cells and the primary cultures of human nasal epithelial cells, the effect and signaling pathway of ASD on MUC8 and MUC5B expressions were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).
ASD increased MUC8 and MUC5B expressions and activated the phosphorylations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited ASD-induced MUC8 and MUC5B expressions. In addition, knockdowns of ERK2 and p38 MAPK by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Toll-like receptor 4 (TLR4) mRNA expression was increased after treatment with ASD. Knockdown of TLR4 by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Furthermore, the phosphorylations of ERK1/2 and p38 MAPK were blocked by knockdown of TLR4.
These results show that ASD induces MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK signaling pathway in human airway epithelial cells.
亚洲沙尘是一种自然现象，起源于中国沙漠，已知含有多种化学和生物分子成分，可加剧气道炎症。气道粘蛋白过度产生是炎症性气道疾病的一项重要病理表现。然而，亚洲沙尘对气道上皮细胞粘蛋白产生的机制尚未阐明。
研究亚洲沙尘对人气道上皮细胞粘蛋白表达的影响及其信号通路。
在NCI-H292细胞和人鼻上皮细胞原代培养物中，使用逆转录聚合酶链反应（RT-PCR）、实时PCR、酶免疫测定以及用几种特异性抑制剂和小干扰RNA（siRNA）进行免疫印迹分析，研究亚洲沙尘对MUC8和MUC5B表达的影响及其信号通路。
亚洲沙尘增加了MUC8和MUC5B的表达，并激活了细胞外信号调节激酶1/2（ERK1/2）和p38丝裂原活化蛋白激酶（MAPK）的磷酸化。U0126（ERK1/2 MAPK抑制剂）和SB203580（p38 MAPK抑制剂）抑制了亚洲沙尘诱导的MUC8和MUC5B表达。此外，siRNA敲低ERK2和p38 MAPK可阻断亚洲沙尘诱导的MUC8和MUC5B mRNA表达。用亚洲沙尘处理后，Toll样受体4（TLR4）mRNA表达增加。siRNA敲低TLR4可阻断亚洲沙尘诱导的MUC8和MUC5B mRNA表达。此外，TLR4敲低可阻断ERK1/2和p38 MAPK的磷酸化。
这些结果表明，亚洲沙尘通过人气道上皮细胞中TLR4依赖的ERK2和p38 MAPK信号通路诱导MUC8和MUC5B表达。
