Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages


Baris E., Efe H., GÜMÜŞTEKİN M., ARICI M. A., TOSUN M.

FRONTIERS IN MOLECULAR BIOSCIENCES, vol.8, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 8
  • Publication Date: 2021
  • Doi Number: 10.3389/fmolb.2021.721533
  • Journal Name: FRONTIERS IN MOLECULAR BIOSCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Directory of Open Access Journals
  • Keywords: varenicline, alpha 7nAChR, inflammation, cytokine, proliferation, migration, IMPROVES SURVIVAL, LIPOPOLYSACCHARIDE, EXPRESSION, MIGRATION, STIMULATION, CELLS, PROLIFERATION, CHEMOKINE, AGONIST, PATHWAY
  • Dokuz Eylül University Affiliated: Yes

Abstract

The 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.