title: Cadmium induces mucin 8 expression via Toll-like receptor 4-mediated extracellular signal related kinase 1/2 and p38 mitogen-activated protein kinase in human airway epithelial cells.
abstract: Inhalation of cadmium can lead to development of inflammatory airway diseases such as acute pulmonary edema and chronic obstructive pulmonary disease. In inflammatory airway diseases, expression of mucins is increased, which leads to increased morbidity and mortality of the affected patients. However, no study on the effect of cadmium on expression of mucin genes in airway epithelial cells has been reported. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of cadmium on expression of mucin genes in human airway epithelial cells.
  
  
  
  In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effect and signaling pathway of cadmium on expression of mucin genes were investigated using reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).
  
  
  
  Cadmium increased mucin 8 (MUC8) expression and Toll-like receptor (TLR) 4 messenger RNA (mRNA) expression. Cadmium significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, TLR4 siRNA, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked cadmium-induced MUC8 mRNA expression. TLR4 siRNA significantly blocked cadmium-activated phosphorylation of ERK1/2 MAPK and p38 MAPK.
  
  
  
  The results of this study suggest for the first time that cadmium induces MUC8 expression via TLR4-mediated ERK1/2 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: 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: 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: Yoon Seok
authors.initials: YS
authors.lastname: Choi
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
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C105059:MUC8 protein, human; D009077:Mucins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D002104:Cadmium; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: ERK1/2 MAPK; MUC8; TLR4; airway epithelial cell; cadmium; p38 MAPK