title: Delphinidin Inhibits LPS-Induced MUC8 and MUC5B Expression Through Toll-like Receptor 4-Mediated ERK1/2 and p38 MAPK in Human Airway Epithelial Cells.
abstract: OBJECTIVE
  Delphinidin is one of the anthocyanidins. It is believed to have anti-inflammatory property including antioxidant, antiangiogenic, and anti-cancer properties. However, the anti-inflammatory effect of delphinidin in mucin-producing human airway epithelial cells has not been determined. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of delphinidin in lipopolysaccharide (LPS)-induced MUC8 and MUC5B expression in human airway epithelial cells.
  
  
  METHODS
  In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay were used for investigating the expressions of MUC8, MUC5, and Toll-like receptor 4 (TLR4), after LPS treatment and delphinidin treatment. And the signaling pathway of delphinidin on LPS-induced MUC8 and MUC5B expression was investigated using the RT-PCR, and immunoblot analysis. To confirm the involvement of TLR4 in LPS-induced MUC8 and MU5B expression, the cells were transfected with TLR4 siRNA.
  
  
  RESULTS
  In NCI-H292 airway epithelial cells, LPS (100 ng/mL) significantly induced TLR4, MUC8, and MUC5B expression. TLR4 siRNA significantly blocked LPS-induced MUC8 and MUC5B mRNA expression. LPS (100 ng/mL) significantly activated the phosphorylation of extracellular signal related kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (MAPK). Delphinidin (50 and 100 µM) inhibited LPS-induced TLR4, MUC8, and MUC5B expression and LPS-induced phosphorylation of ERK1/2 and p38 MAPK. In the primary cultures of normal nasal epithelial cells, delphinidin (50 and 100 µM) significantly inhibited LPS-induced TLR4, MUC8, and MUC5B gene expression.
  
  
  CONCLUSIONS
  These results suggest that delphinidin attenuates LPS-induced MUC8 and MUC5B expression through the TLR4-mediated ERK1/2 and p38 MAPK signaling pathway in human airway epithelial cells. These findings indicated that delphinidin may be a therapeutic agent for control of inflammatory airway diseases.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Bo Sung
authors.initials: BS
authors.lastname: Jeon
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Si-Youn
authors.initials: SY
authors.lastname: Song
authors.affiliation: Department of Otorhinolaryngology-Head and Neck surgery, Yeungnam University College of Medicine, Daegu, Korea. ; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Korea.
authors.forename: Yong-Dae
authors.initials: YD
authors.lastname: Kim
keywords: Airway epithelial cell; Delphinidin; Human MUC5B protein; Human MUC8 protein; Lipopolysaccharides; Toll-like receptor 4