Backgrounds: Varenicline, a selective partial agonist of the a4b2 nicotinic acetylcholine receptor (nAChR) and a full agonist of the a7 nAChR, is a drug for smoking cessation. We previously reported that varenicline protects porcine pancreatic elastase (PPE)-induced alveolar expansion via a7 nAChR. However, the mechanism remains obscure. The aim of this study was to determine whether varenicline shows protective effect on the upregulated expression of osteopontin (OPN) in the alveolar macrophages (MH-S) obtained from lungs of patients with COPD.
Results: The expressions of OPN protein and mRNA were dose-dependently decreased by varenicline treatment for 24 hr; these decreases reached a peak at 10 uM varenicline. Next, to elucidate the mechanisms underlying these effects of varenicline, MH-S macrophages were treated with varenicline and a7 nAChR antagonist. Our results demonstrated that a7 nAChR antagonist reversed varenicline-induced lowered expressions of the OPN protein and mRNA.
Conclusion: These findings suggest that varenicline protects against PPE-damaged lung by downregulating the expressions of OPN protein and mRNA via a7 nAChR in macrophages. Varenicline may be one of the most useful medication for patients with COPD.

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