title: Effect of steroids, acetyl-cysteine and calcium-activated chloride channel inhibitors on allergic mucin expression in sinus mucosa.
abstract: OBJECTIVE
  Allergic inflammation of the upper airways is commonly associated with mucus hypersecretion. At present, there is no specific mucus regulating drug available. Our goal was to investigate the effect of glucocorticosteroids, acetyl-cysteine (ACC), and calcium-activated chloride channel (CLCA) inhibitors in a model of Th2 type cytokine induced mucin expression in human airway mucosa.
  
  
  METHODS
  Prospective.
  
  
  METHODS
  Explanted tissue from human sinus mucosa was stimulated with interleukin (IL)-4, IL-9, or IL-13. Different concentrations of dexamethasone, ACC, or CLCA inhibitors [niflumic acid (NFA) or MSI-2216] were added to stimulated tissue. Epithelial mucin expression was quantified using periodic acid-Schiff staining.
  
  
  RESULTS
  IL-4, IL-9, and IL-13 significantly increased epithelial mucin expression (P < .05). Dexamethasone reduced Th2 type cytokine induced mucin expression in a dose-dependent manner being statistically significant at concentrations >or=4.0 micromol/L (IL-4) and >or=40.0 micromol/L (IL-9 and IL-13) (P < .05). ACC had no significant effect on IL-4 and IL-13 induced mucin expression, whereas IL-9 induced mucin expression was significantly decreased at concentrations >or=3.0 mmol/L (P < .05). NFA and MSI-2216 decreased Th2 type cytokine induced mucin expression in a dose-dependent manner. This effect was statistically significant at concentrations >or=100 micromol/L (NFA) and >or=50 micromol/L (MSI-2216) (P < .05).
  
  
  CONCLUSIONS
  Th2 type cytokines can induce mucin expression in a model of explanted human airway mucosa. Th2 type cytokine induced mucin expression can be effectively reduced by either glucocorticosteroids or CLCA inhibitors ex vivo. Besides glucocorticosteroids CLCA inhibitors may offer an alternative therapeutic approach to treat allergic mucus hypersecretion.
authors.affiliation: From the Medical Clinic, Research Center Borstel, Borstel, Germany. hphauber@web.de
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hauber
authors.forename: Armin
authors.initials: A
authors.lastname: Steffen
authors.forename: Torsten
authors.initials: T
authors.lastname: Goldmann
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Vollmer
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Hung
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Zabel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009077:Mucins / Q000096:biosynthesis* / Q000187:drug effects; D009544:Niflumic Acid / Q000494:pharmacology; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D018118:Chloride Channels; D016207:Cytokines; D005938:Glucocorticoids; D009077:Mucins; D009544:Niflumic Acid; D003907:Dexamethasone; D000111:Acetylcysteine