title: Effect of β-glucan on MUC4 and MUC5B expression in human airway epithelial cells.
abstract: BACKGROUND
  β-Glucan is found in the cell walls of fungi, bacteria, and some plant tissues, and is detected by the innate immune system. Furthermore, this recognition is known to worsen respiratory symptoms in patients with allergic and inflammatory airway diseases. However, the means by which β-glucan affects the secretion of major mucins by human airway epithelial cells has not been elucidated. Therefore, in this study, the effect and signaling pathway of β-glucan on mucins MUC4 and MUC5B were investigated in human airway epithelial cells.
  
  
  METHODS
  In NCI-H292 cells and human normal nasal epithelial cells, the effect and signaling pathway of β-glucan on MUC4 and MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA).
  
  
  RESULTS
  β-Glucan increased MUC4 and MUC5B expression and activated the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). SB203580 (a p38 MAPK inhibitor) and pyrrolidine dithiocarbamate (PDTC; a NF-κB inhibitor) inhibited β-glucan-induced MUC4 and MUC5B expression. In addition, siRNA knockdown of p38 MAPK blocked β-glucan-induced MUC4 and MUC5B mRNA expression and β-glucan-activated phosphorylation of NF-κB. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by β-glucan, and siRNA knockdown of TLR4 blocked β-glucan-induced MUC4 and MUC5B mRNA expression and β-glucan-activated phosphorylation of p38 MAPK and NF-κB.
  
  
  CONCLUSIONS
  These results demonstrate that in human airway epithelial cells β-glucan induces MUC4 and MUC5B expression via the TLR4-p38 MAPK-NF-κB signaling pathway.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.|Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D055264:Mucin-4 / Q000378:metabolism*; D055257:Mucin-5B / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007093:Imidazoles; C524658:MUC4 protein, human; C524578:MUC5B protein, human; D055264:Mucin-4; D055257:Mucin-5B; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: MUC4; MUC5B; NF-κB; TLR4; airway epithelial cell; p38 MAPK; β-glucan