title: Asian sand dust increases MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK in human airway epithelial cells.
abstract: BACKGROUND
  Asian sand dust (ASD) is a natural phenomenon and originates from the deserts of China and is known to contain various chemical and biomolecular components that enhance airway inflammation. The overproduction of airway mucins is an important pathologic finding in inflammatory airway diseases. However, the mechanism of ASD on mucin production of airway epithelial cells has not been elucidated.
  
  
  OBJECTIVE
  To investigate the effect and signaling pathway of ASD on mucin expressions in human airway epithelial cells.
  
  
  METHODS
  In the NCI-H292 cells and the primary cultures of human nasal epithelial cells, the effect and signaling pathway of ASD on MUC8 and MUC5B expressions were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).
  
  
  RESULTS
  ASD increased MUC8 and MUC5B expressions and activated the phosphorylations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited ASD-induced MUC8 and MUC5B expressions. In addition, knockdowns of ERK2 and p38 MAPK by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Toll-like receptor 4 (TLR4) mRNA expression was increased after treatment with ASD. Knockdown of TLR4 by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Furthermore, the phosphorylations of ERK1/2 and p38 MAPK were blocked by knockdown of TLR4.
  
  
  CONCLUSIONS
  These results show that ASD induces MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK signaling pathway in human airway epithelial cells.
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
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
mesh_terms: D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004391:Dust; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D055257:Mucin-5B / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D004391:Dust; C524578:MUC5B protein, human; C105059:MUC8 protein, human; D055257:Mucin-5B; D009077:Mucins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1