title: Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.
abstract: BACKGROUND
  Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse.
  
  
  OBJECTIVE
  To investigate the effect of steroids and N-acetyl-cysteine (NAC) on PA-induced mucus expression.
  
  
  METHODS
  Calu-3 cells and explanted human mucosa from the upper airways were stimulated with either PA, lipopolysaccharide from alginate producing PA (smooth, sPA-LPS) or non-alginate producing PA (rough, rPA-LPS). Dexamethasone (DEX) and NAC were added in different concentrations. Expression of mucin (MUC5AC) gene and mucin protein expression was quantified using PAS (periodic acids Schiff) staining and real time PCR.
  
  
  RESULTS
  PA, sPA-LPS or rPA-LPS significantly induced mucin protein and MUC5AC gene expression in Calu-3 cells and explanted mucosal tissue (P < 0.05). Both DEX and NAC significantly decreased PA-, sPA-LPS- and rPA-LPS-induced mucin protein expression both in vitro and ex vivo (P < 0.05). A significant reduction was also observed for MUC5AC gene expression with the two agents (P < 0.05) except for sPA-LPS-induced mucin gene expression in vitro (P > 0.05).
  
  
  CONCLUSIONS
  Our data show that both an anti-inflammatory drug (DEX) and an anti-oxidative agent (NAC) can attenuate PA-induced mucus expression in human airways. These results support the use of steroids and NAC in clinical practice to treat PA-induced mucus hypersecretion.
authors.affiliation: Division of Pathophysiology of Inflammation, Research Center Borstel, Borstel, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sprenger
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Armin
authors.initials: A
authors.lastname: Steffen
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hauber
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D005100:Expectorants / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D055271:Mucin 5AC / Q000235:genetics; D009093:Mucus / Q000378:metabolism* / Q000382:microbiology; D016133:Polymerase Chain Reaction; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents; D005100:Expectorants; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D003907:Dexamethasone; D000111:Acetylcysteine