title: Multiple dosing of simvastatin inhibits airway mucus production of epithelial cells: implications in the treatment of chronic obstructive airway pathologies.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment.
  
  
  OBJECTIVE
  The aim of the present work was to study the transport of simvastatin (SV) across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production.
  
  
  METHODS
  Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio.
  
  
  RESULTS
  SV was transported through the cell monolayer and 'retained' inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14 days caused a significant inhibition in mucus production.
  
  
  CONCLUSIONS
  These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.
authors.affiliation: Pharmaceutical Department, University of Parma, Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Marin
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.forename: Francesca
authors.initials: F
authors.lastname: Buttini
authors.forename: Mehra
authors.initials: M
authors.lastname: Haghi
authors.forename: Hui Xin
authors.initials: HX
authors.lastname: Ong
authors.forename: Paul
authors.initials: P
authors.lastname: Young
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006880:Hydroxy Acids / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D007249:Inflammation; D009093:Mucus / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D019821:Simvastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013499:Surface Properties; D013696:Temperature; D013997:Time Factors
chemical_list: D006880:Hydroxy Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin