1. Academic Validation
  2. Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages

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

  • Front Mol Biosci. 2021 Oct 12;8:721533. doi: 10.3389/fmolb.2021.721533.
Elif Baris 1 2 Hande Efe 3 Mukaddes Gumustekin 4 Mualla Aylin Arici 4 Metiner Tosun 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Graduate School of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
  • 2 Department of Pharmacology, Faculty of Medicine, Izmir University of Economics, Izmir, Turkey.
  • 3 Department of Medical Biology and Genetics, Graduate School of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
  • 4 Department of Medical Pharmacology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
Abstract

The cholinergic anti-inflammatory pathway plays an important role in controlling inflammation. This study investigated the effects of varenicline, an α7 nicotinic acetylcholine receptor (α7nAChR) 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 α7nAChR antagonist methyllycaconitine citrate. TNFα, IL-1β, 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 TNFα, IL-6, and IL-1β via α7nAChRs 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 α7nAChR. Our data suggest that varenicline inhibits LPS-induced inflammatory response by activating α7nAChRs within the cholinergic anti-inflammatory pathway, reducing the cytokine levels and cell migration.

Keywords

cytokine; inflammation; migration; proliferation; varenicline; α7nAChR.

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