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

Abstract 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. © 2012 Wiley Periodicals, Inc.