Han Demin, Zhou Bing, Cheng Lei, Oh Yun, Li Huabin
Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Laryngoscope. 2006 Nov;116(11):1973-7. doi: 10.1097/01.mlg.0000236078.81313.c8.
The objective of this study was to evaluate the role of p38 MAP-kinase (MAPK) pathway on CLC-3 expression after interleukin-4 (IL-4) induction in primary cultured human nasal epithelial cells (HNECs) from patients with allergic rhinitis (AR).
Cultured HNECs from five patients with AR were treated with IL-4 (20 ng/mL) with or without SB203580, a selective inhibitor of p38 MAPK, at different concentrations and durations. CLC-3 was detected in HNECs by immunohistochemistry and real-time quantitative reverse transcription-polymerase chain reaction. p38 MAPK and phosphorylated p38 MAPK (pp38 MAPK) was examined by Western blotting.
After exposure to SB203580, CLC-3 expression induced by IL-4 was downregulated in HNECs in a concentration and time-dependent manner. This downregulation was associated with a decrease in pp38 MAPK.
These results confirmed that IL-4 can induce CLC-3 production in HNECs with AR through a p38 MAPK-dependent pathway. Inhibitors of p38 MAPK may become an important strategy for the treatment of AR.
本研究旨在评估p38丝裂原活化蛋白激酶（MAPK）信号通路在白细胞介素-4（IL-4）诱导变应性鼻炎（AR）患者原代培养人鼻上皮细胞（HNECs）中氯离子通道蛋白3（CLC-3）表达方面的作用。
用不同浓度和作用时间的IL-4（20 ng/mL）处理5例AR患者的原代培养HNECs，同时加入或不加入p38 MAPK的选择性抑制剂SB203580。采用免疫组织化学和实时定量逆转录-聚合酶链反应检测HNECs中CLC-3的表达。通过蛋白质印迹法检测p38 MAPK和磷酸化p38 MAPK（pp38 MAPK）。
暴露于SB203580后，IL-4诱导的HNECs中CLC-3表达呈浓度和时间依赖性下调。这种下调与pp38 MAPK的减少有关。
这些结果证实IL-4可通过p38 MAPK依赖性途径诱导AR患者的HNECs产生CLC-3。p38 MAPK抑制剂可能成为治疗AR的重要策略。
