α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates DSS-induced intestinal colitis by improving intestinal mucosal barrier function

Abstract

Background and aims Cholinergic output, which could modulate innate immune responses through stimulation of α7 nicotinic acetylcholine receptor (α7nAChR), might be a target to minimize tissue damage in autoimmune disease. GTS-21, a selective α7nAChR agonist, has previously demonstrated to inhibit synovium inflammation in rheumatoid arthritis. In this study, we investigated the effect of GTS-21 on dextran sulfate sodium (DSS)-induced colitis model and its potential mechanism. Methods Male BABL/c mice (n = 32) were randomly divided into four groups: normal control group, DSS-induced colitis group, GTS-21 treatment with or without α7nAChR antagonist α-BGT treatment group. Disease activity index (DAI), histological activity index (HAI) and colonic macroscopic damage were evaluated. Fluorescein isothiocyanate (FITC)–dextran assay was applied to measure intestinal permeability. The expressions of tight junction (TJ) proteins and NF-κB associated proteins were detected by Western blot. Results GTS-21 could decrease DAI scores, HAI scores, intestinal permeability and reduce the intestinal bacterial translocation in DSS-induced colitis group, whereas α7nAChR antagonist α-BGT could impair this protective influence. The expressions of TJ proteins were increased with administration of GTS-21 both in vivo and in vitro. Furthermore, GTS-21 also inhibited the NF-қB activation in intestinal epithelial cells and colitis model, while α-BGT reversed the inhibitory effect. Conclusion The α7nAChR agonist GTS-21 attenuated DSS-induced colitis through increasing expressions of TJ proteins in colon tissues and improved intestinal barrier function, which might be due to modulating NF-қB activation in intestinal epithelial cells.

Protective effect of carbon dots derived from scrambled Coptidis Rhizoma against ulcerative colitis in mice

“…Upon entry into the colonic environment, the positively charged SCR-CDs might adhere to the intestinal epithelial cells (IECs) and become coated with a protein corona containing TJ proteins, which may contribute to the remodeling of the intestinal barrier. To validate this hypothesis, we performed immunofluorescence staining and western blot analysis to detect the expression of intestinal TJ proteins, and the results obtained were consistent with previous research findings ( Ye et al, 2022 ). In Figures 4D–H , Supplementary Figure S3 , it was observed that the protein levels of ZO-1, claudin-1, and occludin were significantly downregulated after the DSS induction ( p < 0.05).…”

Selenium-containing soybean peptides ameliorate intestinal inflammation and modulate gut microbiota dysbacteriosis in DSS-induced ulcerative colitis mice

“…The damaged intestinal mucosa was characterized by shortening of the length of the intestinal mucosal epithelial villi, shedding of the villi, deepening of the crypts, mucosal edema, and massive inflammatory cell infiltration in the lamina propria. 39 In the present experiment, we analyzed the intestinal morphology of each group using H&E staining of paraffin pathological sections (Fig. 3G).…”

VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration

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