Hedgehog signaling regulates the expression levels of inflammatory mediators in cigarette‑induced airway inflammation

Guo,Yi; Shi,Guochao; Wan,Huanying; Zhou,Min

doi:10.3892/mmr.2018.8861

Hedgehog signaling regulates the expression levels of inflammatory mediators in cigarette‑induced airway inflammation

Authors:
- Yi Guo
- Guochao Shi
- Huanying Wan
- Min Zhou
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Affiliations: Department of Pulmonary and Critical Care Medicine, Shanghai Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
Published online on: April 11, 2018 https://doi.org/10.3892/mmr.2018.8861
Pages: 8557-8563

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Abstract

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.

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