title: 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.
authors: Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung City, Taiwan.
authors: Wei-Chun
authors: WC
authors: Wang
authors: Cheng-Yi
authors: CY
authors: Kuo
authors: Bor-Show
authors: BS
authors: Tzang
authors: Han-Min
authors: HM
authors: Chen
authors: Shao-Hsuan
authors: SH
authors: Kao
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D001681:Biological Assay; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D000077191:Wortmannin; D014945:Wound Healing / Q000187:drug effects; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000730:Androstadienes; D002352:Carrier Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles; D015850:Interleukin-6; D018021:Lithium Chloride; D008301:Maleimides; D008840:Microfilament Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D013449:Sulfonamides; D000077191:Wortmannin; D051176:beta Catenin; C575430:FH535; C502658:FSCN1 protein, human; C417521:SB 216763; C000605506:GSK3B protein, human