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PNU-282987 Attenuates Intestinal Epithelial Barrier Dysfunction in LPS-Induced Endotoxemia

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Abstract

PNU-282987, the α7 acetylcholine receptor(α7nAchR) agonist, has been repeatedly reported to play a key role in anti-inflammatory action of multiple disease. However, little is known about its effect on LPS-induced intestinal epithelial barrier dysfunction. This study investigated the protective effects and mechanisms of PNU-282987 on intestinal epithelial barrier dysfunction in lipopolysaccharide(LPS)-induced endotoxemic rats. Endotoxemia models were induced by intraperitoneal injection of 10 mg/kg LPS. In the endotoxemic group, results showed increases in ileum mucosal permeability, ultrastructural damage of tight junction and redistribution of zonula occludens-1, apoptosis of intestinal epithelial cells and caspase-3 activation. These changes were significantly improved after PNU-282987 administration(P < 0.05). Pretreatment with α-bungarotoxin before PNU-282987 administration reversed the effects of PNU-282987(P < 0.05). These results indicate that PNU-282987 exerts protective effects on intestinal epithelial barrier dysfunction in LPS-induced endotoxemic rats, and its mechanism may involve the improvement of zonula occludens-1 and inhibition of enterocyte apoptosis in an α7nAchR-dependent manner.

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Acknowledgments

This work was financially supported by the National Natural Science Foundation of China(NO.81560131).

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Correspondence to Jianguo Li.

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Ying Zhang and Feng Zhou contributed equally to this work.

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Zhang, Y., Zhou, F., Wang, Z. et al. PNU-282987 Attenuates Intestinal Epithelial Barrier Dysfunction in LPS-Induced Endotoxemia. Inflammation (2020). https://doi.org/10.1007/s10753-019-01096-w

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KEY WORDS

  • PNU-282987
  • intestinal permeability
  • zonula occludens-1
  • tight junction
  • apoptosis