RT Journal Article
SR Electronic
T1 Cigarette smoke extract, affecting choline acetyltransferase and muscarinic receptor M3 expression, induces MUC5AC in NCI-H292 cell line
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P3126
VO 42
IS Suppl 57
A1 Mirella Profita
A1 Angela Marina Montalbano
A1 Caterina Di Sano
A1 Giulia Anzalone
A1 Anna Bonanno
A1 Loredana Riccobono
A1 Giusy Daniela Albano
A1 Maria Ferraro
A1 Michael Paul Pieper
A1 Mark Gjomarkaj
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P3126.abstract
AB Cigarette smoke extract (CSE) affects the expression of ChAT and MRs and mucin production in bronchial epithelial cells suggesting a potential link among smoke, non-neuronal cholinergic system components, and mucus overproduction within the airways of COPD subjects.We evaluated the levels of MUC5AC (the predominant mucin produced in human airways), muscarinic receptor M3 (mAChR M3), Choline Acetyltransferase (ChAT), and acetylcholine (ACh) levels and binding in airway epithelial carcinoma cell line NCI-H292 stimulated with CSE. Furthermore, to confirm CSE role in MUC5AC production, we performed experiments of ChAT RNA interference in NCI-H292 stimulated with CSE. Finally, the effect of Tiotropium (Spiriva®) (100 nM), alone or in combination with Salmeterol (SL) and Fluticasone propionate (FP) was tested in this model.NCI-H292 stimulated with CSE (5%) significantly increased the production of MUC5AC, mAChR M3, the expression of ChAT and the expression and binding of ACh in comparison to untreated cells. The key role of ChAT in MUC5AC production was confirmed by RNA interference experiments that abolished the effect of CSE on its production. Finally Tiotropium, together with FP and SL, completely abolished the effect of CSE on MUC5AC production.This study suggests that cigarette smoke affects the expression of non-neuronal components of the cholinergic system in NCI-H292 cell lines increasing MUC5AC production. The anticholinergic treatment, associated with corticosteroids and a long-acting b2-adrenergic receptor agonist, reduces the secretion of this mucin.