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

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2020 Jan 18

PMID 31950323

Citations 3

Authors

Ying Zhang

Feng Zhou

Zhili Wang

Zhifeng Li

Jianguo Li

Affiliations

Soon will be listed here.

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.

Citing Articles

The Novel Insight of Gut Microbiota from Mouse Model to Clinical Patients and the Role of NF-κB Pathway in Polycystic Ovary Syndrome.

Kong F, Huang P, Chen J, Ma Y Reprod Sci. 2024; 31(11):3323-3333.

PMID: 38653859 DOI: 10.1007/s43032-024-01562-3.

Short-Term Intake of Juice Fermented with ATCC 9595 Amended the Outcome of Endotoxemia Induced by Lipopolysaccharide.

Zagmignan A, Mendes Y, Mesquita G, Costa Dos Santos G, Dos Santos Silva L, Sales A Nutrients. 2023; 15(4).

PMID: 36839417 PMC: 9962425. DOI: 10.3390/nu15041059.

The α7 nicotinic acetylcholine receptor agonist PNU-282987 ameliorates sepsis-induced acute kidney injury through CD4+CD25+ regulatory T cells in rats.

Shi X, Li J, Han Y, Wang J, Li Q, Zheng Y Bosn J Basic Med Sci. 2022; 22(6):882-893.

PMID: 35535600 PMC: 9589307. DOI: 10.17305/bjbms.2022.7111.

References

Kong W, Kang K, Gao Y, Liu H, Meng X, Cao Y . GTS-21 Protected Against LPS-Induced Sepsis Myocardial Injury in Mice Through α7nAChR. Inflammation. 2018; 41(3):1073-1083. DOI: 10.1007/s10753-018-0759-x. View

Song X, Li J, Wang Y, Hu Z, Zhou Q, Du Z . The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats. Shock. 2008; 30(4):468-72. DOI: 10.1097/SHK.0b013e31816d5e49. View

Li H, Wang Y, Wang H, Cao W, Yu X, Lu D . Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms. Acta Pharmacol Sin. 2011; 32(11):1364-72. PMC: 4002724. DOI: 10.1038/aps.2011.102. View

Liu Q, Mittal R, Emami C, Iversen C, Ford H, Prasadarao N . Human isolates of Cronobacter sakazakii bind efficiently to intestinal epithelial cells in vitro to induce monolayer permeability and apoptosis. J Surg Res. 2012; 176(2):437-47. PMC: 3323755. DOI: 10.1016/j.jss.2011.10.030. View

Gu L, Li N, Gong J, Li Q, Zhu W, Li J . Berberine ameliorates intestinal epithelial tight-junction damage and down-regulates myosin light chain kinase pathways in a mouse model of endotoxinemia. J Infect Dis. 2011; 203(11):1602-12. DOI: 10.1093/infdis/jir147. View

Salim S, Soderholm J . Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis. 2010; 17(1):362-81. DOI: 10.1002/ibd.21403. View

De-Souza D, Greene L . Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005; 33(5):1125-35. DOI: 10.1097/01.ccm.0000162680.52397.97. View

Andrews N, Faller D . A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells. Nucleic Acids Res. 1991; 19(9):2499. PMC: 329467. DOI: 10.1093/nar/19.9.2499. View

Yasuda T, Takeyama Y, Ueda T, Shinzeki M, Sawa H, Nakajima T . Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal permeability in experimental severe acute pancreatitis. J Surg Res. 2006; 135(1):18-26. DOI: 10.1016/j.jss.2006.02.050. View

10.

Doig C, Sutherland L, Sandham J, Fick G, Verhoef M, Meddings J . Increased intestinal permeability is associated with the development of multiple organ dysfunction syndrome in critically ill ICU patients. Am J Respir Crit Care Med. 1998; 158(2):444-51. DOI: 10.1164/ajrccm.158.2.9710092. View

11.

Dash P, Zhao J, Kobori N, Redell J, Hylin M, Hood K . Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood-Brain Barrier Permeability following Experimental Traumatic Brain Injury. J Neurosci. 2016; 36(9):2809-18. PMC: 4879217. DOI: 10.1523/JNEUROSCI.3197-15.2016. View

12.

Chiu C, McARDLE A, Brown R, Scott H, GURD F . Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg. 1970; 101(4):478-83. DOI: 10.1001/archsurg.1970.01340280030009. View

13.

Ivey R, Desai M, Green K, Sinha-Hikim I, Friedman T, Sinha-Hikim A . Additive effects of nicotine and high-fat diet on hepatocellular apoptosis in mice: involvement of caspase 2 and inducible nitric oxide synthase-mediated intrinsic pathway signaling. Horm Metab Res. 2014; 46(8):568-73. PMC: 4327908. DOI: 10.1055/s-0034-1375610. View

14.

Gao Y, Kang K, Liu H, Kong W, Han Q, Zhang X . GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res. 2017; 9(10):4673-4681. PMC: 5666073. View

15.

Tracey K . Reflex control of immunity. Nat Rev Immunol. 2009; 9(6):418-28. PMC: 4535331. DOI: 10.1038/nri2566. View

16.

Li Q, Zhang Q, Wang C, Liu X, Li N, Li J . Disruption of tight junctions during polymicrobial sepsis in vivo. J Pathol. 2009; 218(2):210-21. DOI: 10.1002/path.2525. View

17.

P Blackwood B, Yuan C, Wood D, Nicolas J, Grothaus J, Hunter C . Probiotic Species Strengthen Intestinal Barrier Function and Tight Junction Integrity in Experimental Necrotizing Enterocolitis. J Probiotics Health. 2017; 5(1). PMC: 5475283. DOI: 10.4172/2329-8901.1000159. View

18.

Rosas-Ballina M, Olofsson P, Ochani M, Valdes-Ferrer S, Levine Y, Reardon C . Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011; 334(6052):98-101. PMC: 4548937. DOI: 10.1126/science.1209985. View

19.

Zanetti F, Giacomello M, Donati Y, Carnesecchi S, Frieden M, Barazzone-Argiroffo C . Nicotine mediates oxidative stress and apoptosis through cross talk between NOX1 and Bcl-2 in lung epithelial cells. Free Radic Biol Med. 2014; 76:173-84. DOI: 10.1016/j.freeradbiomed.2014.08.002. View

20.

Krzyzaniak M, Peterson C, Loomis W, Hageny A, Wolf P, Reys L . Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown. J Trauma. 2011; 70(5):1168-75. PMC: 4241239. DOI: 10.1097/TA.0b013e318216f754. View