title: Diesel Exhaust Particles Enhance MUC4 Expression in NCI-H292 Cells and Nasal Epithelial Cells via the p38/CREB Pathway.
abstract: BACKGROUND
  Diesel exhaust particles (DEPs), the major contributors to air pollution, induce inflammatory responses in the nasal epithelium. Overproduction of airway mucins is an important pathogenic finding in inflammatory airway diseases.
  
  
  OBJECTIVE
  The aims of the present study were to determine the effect of DEPs on the expression of the mucin gene MUC4 and to investigate the underlying mechanism of DEP-induced MUC4 expression in NCI-H292 cells and primary nasal epithelial cells (PNECs).
  
  
  METHODS
  NCI-H292 cells were stimulated for 24 h with DEPs. Messenger RNA (mRNA) and protein expression of MUC4 was determined by real-time reverse transcription (RT) polymerase chain reaction (PCR) and Western blotting. NCI-H292 cells were exposed to 3 mitogen-activated protein kinase inhibitors (U0126, SB203580, and SP600125) and a CREB (cAMP response element-binding protein) inhibitor prior to stimulation with DEPs, and MUC4 expression was examined by RT-PCR and Western blotting. PNECs were pretreated with a p38 inhibitor and CREB inhibitor prior to stimulation with DEPs, and MUC4 expression was then determined by RT-PCR and/or Western blotting.
  
  
  RESULTS
  DEPs significantly increased the expression of MUC4 mRNA and protein. MUC4 mRNA and protein expression was inhibited by pretreatment with p38 and CREB inhibitors in NCI-H292 stimulated with DEPs. p38 and CREB inhibitors also blocked the expression of MUC4 mRNA and protein in DEP-stimulated PNECs.
  
  
  CONCLUSIONS
  We demonstrated that DEPs stimulated the expression of MUC4 via the p38/CREB pathway in NCI-H292 cells and PNECs. The results of the present study pave the way for further studies on the role of MUC4 in DEP-induced hypersecretion in airway epithelium.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Il-Ho
authors.initials: IH
authors.lastname: Park
authors.forename: Ju-Hyung
authors.initials: JH
authors.lastname: Kang
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Shin
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004847:Epithelial Cells; D015870:Gene Expression; D006801:Humans; D055264:Mucin-4 / Q000235:genetics* / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism*; D052638:Particulate Matter / Q000009:adverse effects*; D015398:Signal Transduction; D001335:Vehicle Emissions / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C524658:MUC4 protein, human; D055264:Mucin-4; D052638:Particulate Matter; D001335:Vehicle Emissions; D048051:p38 Mitogen-Activated Protein Kinases