Department of Pulmonary and Critical Care Medicine, Shanghai Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China.
Mol Med Rep. 2018 Jun;17(6):8557-8563. doi: 10.3892/mmr.2018.8861. Epub 2018 Apr 11.
Chronic obstructive pulmonary disease (COPD) is a persistent airway inflammation influenced by cigarette smoke. Previous studies have reported that Hedgehog (Hh) signaling is aberrantly activated by cigarette smoke and dysregulated in COPD. The present study explored the role of the Hh signaling pathway on the expression levels of certain inflammatory mediators in cigarette‑induced airway inflammation. Herein, a total of three A549 cell populations were generated: The A0 group as control cells, the A1 group cells treated with nicotine at a concentration of 10 µM for 12, 24 and 48 h, and the A2 group cultured simultaneously with nicotine and cyclopamine for the same duration. The total concentrations of the inflammatory mediators interleukin‑6 (IL‑6), IL‑8 and tumor necrosis factor (TNF)‑α, and an anti‑inflammatory cytokine, IL‑10, were assessed in all of the cells by ELISA and western blotting. The protein levels of sonic hedgehog (Shh), glioma‑associated oncoprotein 1 (Gli1) and Smoothened (Smo) in nicotine‑induced Hh signaling were also detected. The results indicated that A549 had increased levels of IL‑6, IL‑8 and TNF‑α when cultured with nicotine when compared with the control cells. By contrast, the expression levels of these inflammatory mediators decreased with varying degrees when treated with cyclopamine that blocked the Hh signaling pathway. The IL‑10 expression levels exhibited the reverse. The expressions of the Shh, Gli1 and Smo proteins were higher in the A1 group when compared with the control and decreased with cyclpoamine treatment. In conclusion, the Hh signaling pathway may partly have an impact on cigarette‑induced airway inflammation via the regulation of inflammatory mediators. Thus, blocking Hh signaling and diminishing the airway inflammation reaction may serve as a potential therapy for COPD.
慢性阻塞性肺疾病（COPD）是一种受香烟烟雾影响的持续性气道炎症。先前的研究报告称，Hedgehog（Hh）信号通路受到香烟烟雾的异常激活，并在 COPD 中失调。本研究探讨了 Hh 信号通路对香烟诱导的气道炎症中某些炎症介质表达水平的作用。在此，共生成了三组 A549 细胞群：A0 组作为对照细胞，A1 组细胞用浓度为 10 μM 的尼古丁处理 12、24 和 48 h，A2 组同时用尼古丁和环巴胺培养相同的时间。通过 ELISA 和 Western blot 评估所有细胞中白细胞介素 6（IL-6）、白细胞介素 8（IL-8）和肿瘤坏死因子（TNF）-α的总浓度以及抗炎细胞因子 IL-10。还检测了尼古丁诱导的 Hh 信号通路中 sonic hedgehog（Shh）、神经胶质瘤相关癌基因蛋白 1（Gli1）和 Smoothened（Smo）的蛋白水平。结果表明，与对照细胞相比，用尼古丁培养的 A549 细胞中 IL-6、IL-8 和 TNF-α水平升高。相比之下，当用阻断 Hh 信号通路的环巴胺处理时，这些炎症介质的表达水平呈不同程度下降。IL-10 的表达水平则相反。与对照和环巴胺处理组相比，A1 组中 Shh、Gli1 和 Smo 蛋白的表达更高。总之，Hh 信号通路可能通过调节炎症介质对香烟诱导的气道炎症产生一定影响。因此，阻断 Hh 信号并减少气道炎症反应可能成为 COPD 的一种潜在治疗方法。
