Encenicline, an α7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice
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Encenicline, an α7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice. / Salaga, M; Blomster, L V; Piechota-Polańczyk, A; Zielińska, M; Jacenik, D; Cygankiewicz, A I; Krajewska, W M; Mikkelsen, J D; Fichna, Jakub.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 356, No. 1, 01.2016, p. 157-69.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Encenicline, an α7 Nicotinic Acetylcholine Receptor Partial Agonist, Reduces Immune Cell Infiltration in the Colon and Improves Experimental Colitis in Mice
AU - Salaga, M
AU - Blomster, L V
AU - Piechota-Polańczyk, A
AU - Zielińska, M
AU - Jacenik, D
AU - Cygankiewicz, A I
AU - Krajewska, W M
AU - Mikkelsen, J D
AU - Fichna, Jakub
N1 - Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.
PY - 2016/1
Y1 - 2016/1
N2 - The α7 pentamer nicotinic acetylcholine receptors (nAChRs) are a target in transduction of anti-inflammatory signals from the central nervous system 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 interleukin (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 IHC. In the TNBS model encenicline reduced the frequency of FoxP3(+) IL-17A(+) T cells in the colon. In the DSS-model treatment 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 anticolitic drugs.
AB - The α7 pentamer nicotinic acetylcholine receptors (nAChRs) are a target in transduction of anti-inflammatory signals from the central nervous system 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 interleukin (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 IHC. In the TNBS model encenicline reduced the frequency of FoxP3(+) IL-17A(+) T cells in the colon. In the DSS-model treatment 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 anticolitic drugs.
KW - Animals
KW - Colitis, Ulcerative
KW - Colon
KW - Dextran Sulfate
KW - Flow Cytometry
KW - Forkhead Transcription Factors
KW - Hexamethonium
KW - Interleukin-17
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Nicotinic Agonists
KW - Nicotinic Antagonists
KW - Peroxidase
KW - Quinuclidines
KW - T-Lymphocytes
KW - Thiophenes
KW - Trinitrobenzenesulfonic Acid
KW - alpha7 Nicotinic Acetylcholine Receptor
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1124/jpet.115.228205
DO - 10.1124/jpet.115.228205
M3 - Journal article
C2 - 26462538
VL - 356
SP - 157
EP - 169
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -
ID: 164442907