title: Spleen tyrosine kinase induces MUC5AC expression in human airway epithelial cell.
abstract: BACKGROUND
  MUC5AC, a major secreted mucin, is increased in chronic inflammatory airway disease. Spleen tyrosine kinase (SYK) is a mediator, which acts as an important regulator of intracellular signal transduction in the inflammatory response. SYK was originally identified in hematopoietic cells, and its expression in some nonhematopoietic cells, including respiratory epithelial cells, was recently demonstrated. However, the effects of SYK on mucin secretion in human airway epithelial cells have not been studied. The objective of this study was to investigate the effect and brief signaling pathways of SYK on MUC5AC expression in human airway epithelial cells.
  
  
  METHODS
  In mucin-producing human NCI-H292 cells and primary cultures of human nasal epithelial cells, the effects and signaling pathways of SYK on MUC5AC expression were investigated by reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA).
  
  
  RESULTS
  SYK induced MUC5AC expression. SYK activated significant phosphorylation of extracellular signal-related kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. SYK-induced MUC5AC expression was significantly attenuated by pretreatment with U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor). In addition, the knockdown of ERK2 and p38 MAPK by ERK2 and p38 MAPK siRNA significantly blocked SYK-induced MUC5AC expression.
  
  
  CONCLUSIONS
  These results indicated that SYK increased MUC5AC expression via ERK2 and p38 MAPK signaling pathways 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: Hyung Gyun
authors.initials: HG
authors.lastname: Na
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000072377:Syk Kinase / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D002070:Butadienes; D007093:Imidazoles; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009570:Nitriles; D011725:Pyridines; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C113580:U 0126; C000606896:SYK protein, human; D000072377:Syk Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580