IL-6 augmented motility of airway epithelial cell BEAS-2B via Akt/GSK-3β signaling pathway

Cell migration plays a pivotal role in airway repair and remodeling involved in respiratory diseases such as asthma. Interleukin-6 (IL-6) and fascin-1 are involved in cell migration upon stimulation; however, the roles of IL-6 and fascin-1 in migration of airway epithelial cell remain sketchy. The present study was aimed to investigate influence of IL-6 on cell motility with emphasis on the association with fascin-1. Wound healing assay and transmigration assay were performed to examine effect of IL-6 on migration and invasiveness of human bronchial epithelial cell BEAS-2B. Level of mRNA expression was determined by RT-PCR and quantitative real-time RT-PCR (Q-PCR). Involvement of kinase and transcription factor signaling in IL-6-induced cell migration was investigated using immunoblot and specific inhibitors. IL-6 significantly augmented cell migration and invasiveness in parallel with elevated fascin-1 expression. Further investigation showed that IL-6 dose-dependently upregulated fascin-1 expression in both mRNA and protein levels. We showed that IL-6 activated Akt and inhibited glycogen synthase kinase-3β (GSK-3β), highly associating with fascin-1 mRNA expression. Additionally, IL-6-induced migration was significantly diminished by phosphatidyl inositol 3-phosphate kinase (PI3K) inhibitor (wortamannin) and β-catenin inhibitor FH535. Moreover, LiCl and SB216763, inhibitors of GSK-3β augmented cell migration as well as fascin-1 mRNA expression. Conclusively, these findings reveal that IL-6-induced migration of BEAS-2B cell may be attributed to activation of Akt, inhibition of GSK-3β, and the associated increase of β-catenin and fascin-1 expression, indicating an important role of Akt/GSK-3β signaling and β-catenin/fascin-1 in IL-6 associated airway remodeling. J. Cell. Biochem. 113: 3567-3575, 2012.