RT Journal Article SR Electronic T1 Encenicline, a α7 nicotinic acetylcholine receptor partial agonist, reduces immune cell infiltration in the colon and improves experimental colitis in mice JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.115.228205 DO 10.1124/jpet.115.228205 A1 Maciej Salaga A1 Linda V Blomster A1 Aleksandra Piechota-Polańczyk A1 Marta Zielinska A1 Damian Jacenik A1 Adam I Cygankiewicz A1 Wanda M Krajewska A1 Jens D Mikkelsen A1 Jakub Fichna YR 2015 UL http://jpet.aspetjournals.org/content/early/2015/10/13/jpet.115.228205.abstract AB The α7 pentamer nicotinic acetylcholine receptors (nAChRs) are a target in transduction of anti-inflammatory signals from the central nervous system (CNS) to the gastrointestinal (GI) tract. The aim of this study was to investigate the anti-inflammatory action of the novel α7 nAChR partial agonist, encenicline and to determine the mechanism underlying its activity. Anti-inflammatory activity of encenicline was evaluated using trinitrobenzenesulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced models of colitis. Macroscopic score, ulcer score, colon length and thickness, as well as myeloperoxidase (MPO) activity were recorded. Immunohistochemistry (IHC) was used to measure the infiltration of immune cells in the colon. Furthermore, we employed flow cytometry to determine the effect of encenicline on frequencies of FoxP3+ and IL-17A+ T cells in the mouse colon. Encenicline attenuated TNBS- and DSS-induced colitis in mice via α7 nAChRs, as indicated by significantly reduced macroscopic parameters and MPO activity. Treatment with encenicline significantly reduced the infiltration of macrophages, neutrophils and B cells in the colon of TNBS-treated animals, as indicated by the IHC. In the TNBS model encenicline reduced the frequency of FoxP3+ IL-17A+ T cells in the colon. In the DSS model treatment with encenicline increased the frequency of FoxP3+ T cells and reduced IL-17A+ T cells. Stimulation of α7 nAChR with partial agonist encenicline alleviates colitis via alteration of the number and/or activation status of the immune cells in the gut, emphasizing a potential role of α7 nAChRs as a target for anti-colitic drugs.