The effect of quercetin on human neutrophil elastase-induced mucin5AC expression in human airway epithelial cells

Int Immunopharmacol. 2012 Oct;14(2):195-201. doi: 10.1016/j.intimp.2012.07.008. Epub 2012 Jul 21.

Abstract

Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. Mucus hypersecretion is a common pathological change in chronic inflammatory diseases of the airway. We investigated the effect of quercetin on mucin 5AC (MUC5AC) expression induced by human neutrophil elastase (HNE) in airway epithelial cells and its molecular mechanisms. Human airway epithelial (HBE16) cells were pretreated with quercetin and were treated with HNE. We found that HNE induced a significant increase in the levels of MUC5AC and EGFR in cells treated only with HNE. Quercetin suppressed gene transcription and protein expression of MUC5AC in a dose-dependent manner, with significant inhibition from 40 μM. mRNA and protein expressions of EGFR decreased markedly when pretreated with quercetin. Among three MAPK proteins, only phosphorylated ERK1/2 protein expression increased significantly after treatment with HNE alone and decreased significantly after pretreatment with quercetin. HNE also activated phosphorylated PKC protein expression which was attenuated when pretreated with quercetin. These results suggest that quercetin can inhibit HNE-induced MUC5AC expression in human airway epithelial cells through PKC/EGFR/ERK signal transduction pathway. In the future, quercetin might be a valuable treatment for mucin hypersecretion in chronic inflammatory airway diseases in clinic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Leukocyte Elastase / metabolism
  • Mucin 5AC / biosynthesis*
  • Mucin 5AC / genetics
  • Quercetin / pharmacology*
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / immunology
  • Secretory Pathway / drug effects
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Mucin 5AC
  • Quercetin
  • EGFR protein, human
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • Leukocyte Elastase