PT  - JOURNAL ARTICLE
AU  - J. Cortijo
AU  - M. Mata
AU  - J. Milara
AU  - E. Donet
AU  - A. Gavaldà
AU  - M. Miralpeix
AU  - E.J. Morcillo
TI  - Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways
AID  - 10.1183/09031936.00182009
DP  - 2011 Feb 01
TA  - European Respiratory Journal
PG  - 244--254
VI  - 37
IP  - 2
4099  - http://erj.ersjournals.com/content/37/2/244.short
4100  - http://erj.ersjournals.com/content/37/2/244.full
SO  - Eur Respir J2011 Feb 01; 37
AB  - Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect of aclidinium, a new long-acting muscarinic antagonist, on MUC5AC expression in human airway epithelial cells. MUC5AC mRNA (RT-PCR) and protein expression (ELISA and immunohistochemistry) were studied in human bronchial tissue and differentiated human airway epithelial cells activated with carbachol (100 μM) or cigarette smoke extract in the absence or presence of aclidinium. Carbachol increased MUC5AC mRNA and protein expression in human bronchus and cultured epithelial cells. Aclidinium inhibited the carbachol-induced MUC5AC mRNA and protein expression with potency (half maximal inhibitory concentration) ∼1 nM in human bronchus and cultured airway epithelial cells. AG1478, a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, inhibited carbachol-induced MUC5AC responses, indicating EGFR transactivation. Aclidinium inhibited carbachol-induced phospho-EGFR and phospho-p44/42 MAPK expression. In cultured airway epithelial cells transfected with small interfering (si)RNA against muscarinic receptor subtypes, siRNA-M3 but not siRNA-M2 blocked carbachol-induced MUC5AC expression. Cigarette smoke-induced MUC5AC upregulation in cultured airway epithelial cells was suppressed by aclidinium. In conclusion, aclidinium decreases carbachol and tobacco smoke-induced MUC5AC overexpression in human airway epithelial cells. This effect may contribute to the clinical efficacy of aclidinium in mucus hypersecretory diseases including COPD.