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. 2014 May 30;448(2):231-5. doi: 10.1016/j.bbrc.2014.04.100. Epub 2014 Apr 30.
Thymic stromal lymphopoietin (TSLP) is an interleukin 7-like cytokine and a potent factor for B- and T-cell growth and differentiation. Recent studies have demonstrated an association of TSLP with allergic and inflammatory airway diseases. However, no study on the effect of TSLP on expression of mucin genes in airway epithelial cells has been reported. Therefore, the effects and brief signaling pathways of TSLP on expression of mucin genes in human airway epithelial cells were investigated in this study. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of TSLP on expression of mucin genes 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). In human NCI-H292 airway epithelial cells, TSLP increased MUC5B expression. TSLP significantly activated phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) significantly attenuated TSLP-induced MUC5B mRNA expression. Knockdown of ERK1, ERK2, and p38 MAPK by ERK1, ERK2, and p38 MAPK siRNA significantly blocked TSLP-induced MUC5B mRNA expression. In the primary cultures of normal nasal epithelial cells, TSLP significantly increased MUC5B mRNA expression, which was significantly attenuated after pretreatment with U0126 and SB203580. These results suggest that TSLP induces MUC5B expression via the ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells.
胸腺基质淋巴细胞生成素（TSLP）是一种白细胞介素 7 样细胞因子，是 B 细胞和 T 细胞生长和分化的有力因子。最近的研究表明，TSLP 与过敏性和炎症性气道疾病有关。然而，目前还没有研究表明 TSLP 对气道上皮细胞粘蛋白基因表达的影响。因此，本研究探讨了 TSLP 对人气道上皮细胞粘蛋白基因表达的影响及其短暂的信号通路。在粘蛋白产生的人 NCI-H292 气道上皮细胞和正常鼻上皮细胞的原代培养物中，通过逆转录-聚合酶链反应（RT-PCR）、实时 PCR、酶联免疫吸附试验以及几种特定抑制剂和小干扰 RNA（siRNA）的免疫印迹分析，研究了 TSLP 对粘蛋白基因表达的影响及其信号通路。在人 NCI-H292 气道上皮细胞中，TSLP 增加了 MUC5B 的表达。TSLP 显著激活了 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）显著减弱了 TSLP 诱导的 MUC5B mRNA 表达。ERK1、ERK2 和 p38 MAPK 的 siRNA 敲低显著阻断了 TSLP 诱导的 MUC5B mRNA 表达。在正常鼻上皮细胞的原代培养物中，TSLP 显著增加了 MUC5B mRNA 表达，而 U0126 和 SB203580 预处理后，这种表达显著减弱。这些结果表明，TSLP 通过 ERK1/2 和 p38 MAPK 信号通路诱导人气道上皮细胞中 MUC5B 的表达。
