Baris, ElifEfe, HandeGumustekin, MukaddesArici, Mualla AylinTosun, Metiner2023-06-162023-06-1620212296-889Xhttps://doi.org/10.3389/fmolb.2021.721533https://hdl.handle.net/20.500.14365/2506The cholinergic anti-inflammatory pathway plays an important role in controlling inflammation. This study investigated the effects of varenicline, an alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) agonist, on inflammatory cytokine levels, cell proliferation, and migration rates in a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 murine macrophage cell lines. The cells were treated with increasing concentrations of varenicline, followed by LPS incubation for 24 h. Prior to receptor-mediated events, anti-inflammatory effects of varenicline on different cytokines and chemokines were investigated using a cytokine array. Nicotinic AChR-mediated effects of varenicline were investigated by using a non-selective nAChR antagonist mecamylamine hydrochloride and a selective alpha 7nAChR antagonist methyllycaconitine citrate. TNF alpha, IL-1 beta, and IL-6 levels were determined by the ELISA test in cell media 24 h after LPS administration and compared with those of dexamethasone. The rates of cellular proliferation and migration were monitored for 24 h after drug treatment using a real-time cell analysis system. Varenicline decreased LPS-induced cytokines and chemokines including TNF alpha, IL-6, and IL-1 beta via alpha 7nAChRs to a similar level that observed with dexamethasone. Varenicline treatment decreased LPS-induced cell proliferation, without any nAChR involvement. On the other hand, the LPS-induced cell migration rate decreased with varenicline via alpha 7nAChR. Our data suggest that varenicline inhibits LPS-induced inflammatory response by activating alpha 7nAChRs within the cholinergic anti-inflammatory pathway, reducing the cytokine levels and cell migration.eninfo:eu-repo/semantics/openAccessvareniclinealpha 7nAChRinflammationcytokineproliferationmigrationImproves SurvivalLipopolysaccharideExpressionMigrationStimulationCellsProliferationChemokineAgonistPathwayArticle10.3389/fmolb.2021.7215332-s2.0-85118774273