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Effect of Steroids, Acetyl‐cysteine and Calcium‐Activated Chloride Channel Inhibitors on Allergic Mucin Expression in Sinus Mucosa
Author(s) -
Hauber HansPeter,
Steffen Armin,
Goldmann Torsten,
Vollmer Ekkehard,
Hung HsiaoLing,
Wollenberg Barbara,
Zabel Peter
Publication year - 2008
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/mlg.0b013e31817b0732
Subject(s) - mucin , niflumic acid , mucus , medicine , cytokine , endocrinology , interleukin 13 , pharmacology , immunology , interleukin , biology , pathology , ecology
Objectives/Hypothesis: 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. Study Design: 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‐dependant manner being statistically significant at concentrations ≥4.0 μmol/L (IL‐4) and ≥40.0 μmol/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 ≥3.0 mmol/L ( P < .05). NFA and MSI‐2216 decreased Th2 type cytokine induced mucin expression in a dose‐dependant manner. This effect was statistically significant at concentrations ≥100 μmol/L (NFA) and ≥50 μmol/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.