Abstract
Cigarette smoking, contributes to lung remodeling in chronic obstructive pulmonary disease (COPD). As part of remodeling, peribronchiolar fibrosis is observed in small airways of COPD patients and contributes to airway obstruction. Fibroblast to myofibroblast transition is a key step of the peribronchiolar fibrosis formation. This in vitro study examines the effect of cigarette smoke on bronchial fibroblast to myofibroblast transition, and whether aclidinium bromide inhibits this process. Human bronchial fibroblasts were incubated with aclidinium bromide (10−9 M–10−7 M) and exposed to cigarette smoke extract. Collagen type I and alpha-smooth muscle actin expression were measured by real-time PCR and Western blotting as myofibroblast markers. Intracellular reactive oxygen species, cAMP, ERK 1/2 and choline acetyltransferase were measured as intracellular signaling mediators. Cigarette-smoke-induced collagen type I and alpha-smooth muscle actin was mediated by the production of reactive oxygen species, the depletion of intracellular cAMP and the increase of ERK1/2 phosphorylation and choline acetyltransferase. These effects could be reversed by treatment with the anticholinergic aclidinium bromide, by silencing mRNA at muscarinic receptors M1, M2 or M3, or by the depletion of extracellular acetylcholine by treatment with acetylcholinesterase. Non-neuronal cholinergic system is implicated in cigarette smoke-induced bronchial fibroblast to myofibroblast transition which is inhibited by aclidinium bromide.
- ERS