Browse > Article
http://dx.doi.org/10.4196/kjpp.2021.25.4.375

Sepsis induces variation of intestinal barrier function in different phase through nuclear factor kappa B signaling  

Cao, Ying-Ya (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Wang, Zhong-Han (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Xu, Qian-Cheng (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Chen, Qun (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Wang, Zhen (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Lu, Wei-Hua (Department of Intensive Care Unit, The First Affiliated Hospital of Wannan Medical College)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.25, no.4, 2021 , pp. 375-383 More about this Journal
Abstract
The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.
Keywords
Apoptosis; Cell proliferation; Intestinal epithelium; NF-kappa B; Sepsis;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415-418.   DOI
2 Gehart H, Clevers H. Tales from the crypt: new insights into intestinal stem cells. Nat Rev Gastroenterol Hepatol. 2019;16:19-34.   DOI
3 Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, Karatza E, Zisimopoulos D, Maroulis I, Kontogeorgou E, Georgiou CD, Scopa CD, Thomopoulos KC. Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis. Ann Hepatol. 2013;12:301-307.   DOI
4 Obermuller B, Frisina N, Meischel M, Singer G, Stanzl-Tschegg S, Lichtenegger H, Kolb D, Klymiuk I, Till H, Castellani C. Examination of intestinal ultrastructure, bowel wall apoptosis and tight junctions in the early phase of sepsis. Sci Rep. 2020;10:11507.   DOI
5 Li GX, Wang XM, Jiang T, Gong JF, Niu LY, Li N. Berberine prevents damage to the intestinal mucosal barrier during early phase of sepsis in rat through mechanisms independent of the NOD-like receptors signaling pathway. Eur J Pharmacol. 2014;730:1-7.   DOI
6 Dong LW, Yang J, Tong LJ, Tang C, Liu MS. Transcriptional regulation of alpha1-adrenoceptor gene in the rat liver during different phases of sepsis. Biochim Biophys Acta. 1999;1453:207-215.   DOI
7 Maitra SR, Wojnar MM, Lang CH. Alterations in tissue glucose uptake during the hyperglycemic and hypoglycemic phases of sepsis. Shock. 2000;13:379-385.   DOI
8 Remick DG, Bolgos GR, Siddiqui J, Shin J, Nemzek JA. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock. 2002;17:463-467.   DOI
9 Turnbull IR, Javadi P, Buchman TG, Hotchkiss RS, Karl IE, Coopersmith CM. Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels. Shock. 2004;21:121-125.
10 Walley KR, Lukacs NW, Standiford TJ, Strieter RM, Kunkel SL. Balance of inflammatory cytokines related to severity and mortality of murine sepsis. Infect Immun. 1996;64:4733-4738.   DOI
11 Ruiz S, Vardon-Bounes F, Merlet-Dupuy V, Conil JM, Buleon M, Fourcade O, Tack I, Minville V. Sepsis modeling in mice: ligation length is a major severity factor in cecal ligation and puncture. Intensive Care Med Exp. 2016;4:22.   DOI
12 Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109 Suppl:S81-S96.   DOI
13 Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344-362.   DOI
14 Spehlmann ME, Eckmann L. Nuclear factor-kappa B in intestinal protection and destruction. Curr Opin Gastroenterol. 2009;25:92-99.   DOI
15 Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1:a001651.   DOI
16 Chen F, Castranova V, Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 2001;159:387-397.   DOI
17 Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R. Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer. 2004;101:2351-2362.   DOI
18 Bergmann MW, Loser P, Dietz R, von Harsdorf R. Effect of NF-kappa B inhibition on TNF-alpha-induced apoptosis and downstream pathways in cardiomyocytes. J Mol Cell Cardiol. 2001;33:1223-1232.   DOI
19 Fujioka S, Schmidt C, Sclabas GM, Li Z, Pelicano H, Peng B, Yao A, Niu J, Zhang W, Evans DB, Abbruzzese JL, Huang P, Chiao PJ. Stabilization of p53 is a novel mechanism for proapoptotic function of NF-kappaB. J Biol Chem. 2004;279:27549-27559.   DOI
20 Co NN, Tsang WP, Tsang TY, Yeung CL, Yau PL, Kong SK, Kwok TT. AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells. Oncol Rep. 2010;24:547-554.
21 Yang DW, Qian GB, Jiang MJ, Wang P, Wang KZ. Inhibition of microRNA-495 suppresses chondrocyte apoptosis through activation of the NF-κB signaling pathway by regulating CCL4 in osteoarthritis. Gene Ther. 2019;26:217-229.   DOI
22 Fischer A, Gluth M, Pape UF, Wiedenmann B, Theuring F, Baumgart DC. Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2013;304:G970-G979.   DOI
23 Gunther C, Buchen B, Neurath MF, Becker C. Regulation and pathophysiological role of epithelial turnover in the gut. Semin Cell Dev Biol. 2014;35:40-50.   DOI
24 Gunther C, Neumann H, Neurath MF, Becker C. Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut. 2013;62:1062-1071.   DOI
25 Klingensmith NJ, Coopersmith CM. The gut as the motor of multiple organ dysfunction in critical illness. Crit Care Clin. 2016;32:203-212.   DOI
26 Chen LW, Chen PH, Chang WJ, Wang JS, Karin M, Hsu CM. IKappaB-kinase/nuclear factor-kappaB signaling prevents thermal injury-induced gut damage by inhibiting c-Jun NH2-terminal kinase activation. Crit Care Med. 2007;35:1332-1340.   DOI
27 Eslamian G, Ardehali SH, Vahdat Shariatpanahi Z. Association of intestinal permeability with a NUTRIC score in critically ill patients. Nutrition. 2019;63-64:1-8.   DOI
28 Mittal R, Coopersmith CM. Redefining the gut as the motor of critical illness. Trends Mol Med. 2014;20:214-223.   DOI
29 Assimakopoulos SF, Triantos C, Thomopoulos K, Fligou F, Maroulis I, Marangos M, Gogos CA. Gut-origin sepsis in the critically ill patient: pathophysiology and treatment. Infection. 2018;46:751-760.   DOI
30 Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, Welz P, Corona T, Walczak H, Weih F, Klein U, Kelliher M, Pasparakis M. NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions. Immunity. 2016;44:553-567.   DOI
31 Li Q, Zhang Q, Wang C, Liu X, Li N, Li J. Disruption of tight junctions during polymicrobial sepsis in vivo. J Pathol. 2009;218:210-221.   DOI
32 Hu Q, Ren H, Li G, Wang D, Zhou Q, Wu J, Zheng J, Huang J, Slade DA, Wu X, Ren J. STING-mediated intestinal barrier dysfunction contributes to lethal sepsis. EBioMedicine. 2019;41:497-508.   DOI
33 Haussner F, Chakraborty S, Halbgebauer R, Huber-Lang M. Challenge to the intestinal mucosa during sepsis. Front Immunol. 2019;10:891.   DOI
34 Cao YY, Wang Z, Wang ZH, Jiang XG, Lu WH. Inhibition of miR-155 alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling. Int Immunopharmacol. 2021;90:107218.   DOI
35 Li X, Li X, Zheng Z, Liu Y, Ma X. Unfractionated heparin suppresses lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human microvascular endothelial cells by blocking Kruppel-like factor 5 and nuclear factor-κB pathway. Immunobiology. 2014;219:778-785.   DOI
36 Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43:304-377.   DOI
37 Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. 2016;353:i1585.   DOI
38 Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014;5:4-11.   DOI
39 Wullaert A, Bonnet MC, Pasparakis M. NF-κB in the regulation of epithelial homeostasis and inflammation. Cell Res. 2011;21:146-158.   DOI
40 Kondylis V, Kumari S, Vlantis K, Pasparakis M. The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation. Immunol Rev. 2017;277:113-127.   DOI
41 Li GX, Wang XM, Jiang T, Gong JF, Niu LY, Li N. Berberine prevents intestinal mucosal barrier damage during early phase of sepsis in rat through the toll-like receptors signaling pathway. Korean J Physiol Pharmacol. 2015;19:1-7.   DOI
42 Cao Y, Chen Q, Wang Z, Yu T, Wu J, Jiang X, Jin X, Lu W. PLK1 protects against sepsis-induced intestinal barrier dysfunction. Sci Rep. 2018;8:1055.   DOI
43 Yoseph BP, Klingensmith NJ, Liang Z, Breed ER, Burd EM, Mittal R, Dominguez JA, Petrie B, Ford ML, Coopersmith CM. Mechanisms of intestinal barrier dysfunction in sepsis. Shock. 2016;46:52-59.   DOI
44 de Sousa E Melo F, de Sauvage FJ. Cellular plasticity in intestinal homeostasis and disease. Cell Stem Cell. 2019;24:54-64.   DOI
45 Yang S, Zhou M, Fowler DE, Wang P. Mechanisms of the beneficial effect of adrenomedullin and adrenomedullin-binding protein-1 in sepsis: down-regulation of proinflammatory cytokines. Crit Care Med. 2002;30:2729-2735.   DOI
46 Gao MY, Chen L, Yang L, Yu X, Kou JP, Yu BY. Berberine inhibits LPS-induced TF procoagulant activity and expression through NF-κB/p65, Akt and MAPK pathway in THP-1 cells. Pharmacol Rep. 2014;66:480-484.   DOI
47 Peuker K, Muff S, Wang J, Kunzel S, Bosse E, Zeissig Y, Luzzi G, Basic M, Strigli A, Ulbricht A, Kaser A, Arlt A, Chavakis T, van den Brink GR, Schafmayer C, Egberts JH, Becker T, Bianchi ME, Bleich A, Rocken C, et al. Epithelial calcineurin controls microbiota-dependent intestinal tumor development. Nat Med. 2016;22:506-515.   DOI