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DOP090 The α7 nicotinic acetylcholine receptor agonist GTS-21 attenuate DSS-induced colitis by improving intestinal mucosal barrier function

Zhang H.*1, Zhu Y.2

1the First Affiliated Hospital of Nanjing Medical University, Gastroenterology, Nanjing, China 2the First Affiliated Hospital of Nanjing Medical University, Nanjing, China

Background

GTS-21, a selective alpha7-nicotinic acetylcholine receptor (α7nAChR) agonist, demonstrated to inhibit the inflammation. In this study, we investigate whether GTS-21 can protect against DSS-induced colitis and its potential mechanism.

Methods

male BABL/c mice (8-week old) were divided into 4 groups (n=8, each group): control group, DSS group (drank 3.5% DSS), GTS-21 group (drank 3.5%DSS+GTS-21 20mg/kg ip), α-BGT group (3.5% DSS+pre-treated with a-BGT prior to GTS-21). Disease activity index and colonic damage were determined. The intestinal permeability was measured by fluorescein-isothiocyanate-dextran (FITC-Dextran) method. Caco2 cells were used to further investigate the effect of GTS-21 on TJ proteins distibution and NF-κB activity.

Western blot detected the tight junction protein and NF-κB associated protein expression.

Results

1. GTS-21 attenuated DSS-induced colitis, while α7nAChR antagonist α-BGT eliminate protective effects (Fig. 1).

Figure 1

2. GTS-21 attenuated intestinal permeability (p<0.05), and also reduced intestinal bacterial translocation in DSS-induced mice (Fig. 2).

Figure 2

3. The expressions and distribution of tight junction protein were enhanced in DSS-induced mice with GTS-21 treatment (Fig. 3).

Figure 3

4. GTS-21 decreased the NF-κB activation, while α-BGT reversed this inhibitory effect (Fig. 4).

Figure 4

5. GTS-21 improved intestinal epithelial barrier defects (Fig. 5), and reduced nuclear translocation of NF-κB in Caco2 cells induced by TNF-α (Fig. 6).

Figure 5

Figure 6

Conclusion

The α7 nicotinic acetylcholine receptors agonist GTS-21 can attenuate DSS-induced colitis, which might be due to improving intestinal mucosal barrier function.