Skip to main content
Top
Published in: Journal of Inflammation 1/2015

Open Access 01-12-2015 | Research

Crude extract of hydatid laminated layer from Echinococcus granulosus cyst attenuates mucosal intestinal damage and inflammatory responses in Dextran Sulfate Sodium induced colitis in mice

Authors: Imene Soufli, Ryma Toumi, Hayet Rafa, Manel Amri, Moussa Labsi, Lila Khelifi, Ferdinando Nicoletti, Chafia Touil-Boukoffa

Published in: Journal of Inflammation | Issue 1/2015

Login to get access

Abstract

Background

Inflammatory bowel disease is an immunologically mediated disease. Notably, it is less common in countries where there is a greater risk of exposure to helminths. In our study, we examined the modulatory effect of the laminated layer extracted from the cyst wall of a helminth parasite, Echinococcus granulosus, on dextran sulfate sodium (DSS)-induced colitis in mice.

Methods

An acute colitis was induced in BALB/c mice using 2.5% w/v DSS in drinking water. The crude extract of E. granulosus laminated layer was injected intraperitoneally daily, starting 3 days before colitis induction. The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Nitric oxide (NO) and cytokine levels (interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10)) were assessed by enzyme-linked immunosorbent assay. In addition, the colonic expression of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) was examined. Statistical analyses were performed by one-way analysis of variance and the survival rate was analyzed by the long rank test.

Results

Hydatid laminated layer pretreatment significantly improved the clinical symptoms and histological scores (*** p < 0.01) observed during DSS-induced colitis and maintained mucus production by goblet cells. Furthermore, treatment with hydatid laminated layer caused a significant decrease in NO, IFN-γ (** p < 0.01) and TNF-α production (* p < 0.05) and an increase in IL-10 production. These results were associated with localized downregulation of iNOS and NF-κB expression.

Conclusions

Our results demonstrate the potent anti-inflammatory effects of hydatid laminated layer. Furthermore, preventive treatment with the laminated layer played a beneficial role in maintaining the integrity of the intestinal mucosal barrier against DSS-induced injury.
Literature
1.
go back to reference Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390–407.CrossRefPubMed Sartor RB. Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390–407.CrossRefPubMed
2.
go back to reference Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nat. 2007;448:427–34.CrossRef Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nat. 2007;448:427–34.CrossRef
3.
go back to reference Abraham C, Ruslan M. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterol. 2011;140:1729–37. doi:10.1053/j.gastro.2011.02.012.CrossRef Abraham C, Ruslan M. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterol. 2011;140:1729–37. doi:10.1053/j.gastro.2011.02.012.CrossRef
4.
go back to reference Dijkstra G, Moshage H, Van Dullemen HM, de Jager-Krikken A, Tiebosch AT, Kleibeuker JH, et al. Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease. J Pathol. 1998;86:416–21.CrossRef Dijkstra G, Moshage H, Van Dullemen HM, de Jager-Krikken A, Tiebosch AT, Kleibeuker JH, et al. Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease. J Pathol. 1998;86:416–21.CrossRef
5.
go back to reference Kolios G, Brown Z, Robson RL, Robertson DA, Westwick J. Inducible nitric oxide synthase activity and expression in a human colonic epithelial cell line, HT-29. Br J Pharmacol. 1995;116:2866–72.CrossRefPubMedCentralPubMed Kolios G, Brown Z, Robson RL, Robertson DA, Westwick J. Inducible nitric oxide synthase activity and expression in a human colonic epithelial cell line, HT-29. Br J Pharmacol. 1995;116:2866–72.CrossRefPubMedCentralPubMed
6.
go back to reference Kimura H, Miura S, Shigematsu T, Ohkubo N, Tsuzuki Y, Kurose I, et al. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn’s disease. Dig Dis Sci. 1997;42:1047–54.CrossRefPubMed Kimura H, Miura S, Shigematsu T, Ohkubo N, Tsuzuki Y, Kurose I, et al. Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn’s disease. Dig Dis Sci. 1997;42:1047–54.CrossRefPubMed
7.
go back to reference Rafa H, Amri M, Saoula H, Belkhelfa M, Medjeber O, Boutaleb A, et al. Involvement of interferon-γ in bowel disease pathogenesis by nitric oxide pathway: a study in algerian patients. J Interferon Cytokine Res. 2010;30:691–7.CrossRefPubMed Rafa H, Amri M, Saoula H, Belkhelfa M, Medjeber O, Boutaleb A, et al. Involvement of interferon-γ in bowel disease pathogenesis by nitric oxide pathway: a study in algerian patients. J Interferon Cytokine Res. 2010;30:691–7.CrossRefPubMed
8.
go back to reference Abdelouhab K, Rafa H, Toumi R, Bouaziz S, Medjeber O, Touil-Boukoffa C. Mucosal intestinal alteration in experimental colitis correlates with nitric oxide production by peritoneal macrophages: Effect of probiotics and prebiotics. Immunopharmacol Immunotoxicol. 2011;34:590–7. doi:10.3109/08923973.2011.641971.CrossRef Abdelouhab K, Rafa H, Toumi R, Bouaziz S, Medjeber O, Touil-Boukoffa C. Mucosal intestinal alteration in experimental colitis correlates with nitric oxide production by peritoneal macrophages: Effect of probiotics and prebiotics. Immunopharmacol Immunotoxicol. 2011;34:590–7. doi:10.3109/08923973.2011.641971.CrossRef
9.
go back to reference Toumi R, Abdelouhab K, Rafa H, Soufli I, Raissi-Kerboua D, Djeraba Z, et al. Beneficial role of the probiotic mixture Ultrabiotique on maintaining the integrity of intestinal mucosal barrier in DSS-induced experimental colitis. Immunopharmacol Immunotoxicol. 2013;35:403–9. doi:10.3109/08923973.2013.790413.CrossRefPubMed Toumi R, Abdelouhab K, Rafa H, Soufli I, Raissi-Kerboua D, Djeraba Z, et al. Beneficial role of the probiotic mixture Ultrabiotique on maintaining the integrity of intestinal mucosal barrier in DSS-induced experimental colitis. Immunopharmacol Immunotoxicol. 2013;35:403–9. doi:10.3109/08923973.2013.790413.CrossRefPubMed
10.
go back to reference Loftus Jr EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterol. 2004;126:1504–17.CrossRef Loftus Jr EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterol. 2004;126:1504–17.CrossRef
11.
go back to reference Weinstock JV, Elliott DE. Helminths and the IBD hygiene hypothesis. Inflamm Bowel Dis. 2009;15:128–33. doi:10.1002/ibd.20633.CrossRefPubMed Weinstock JV, Elliott DE. Helminths and the IBD hygiene hypothesis. Inflamm Bowel Dis. 2009;15:128–33. doi:10.1002/ibd.20633.CrossRefPubMed
12.
go back to reference Laclotte C, Oussalah A, Rey P, Bensenane M, Pluvinage N, Chevaux JB, et al. Helminths and inflammatory bowel diseases. Gastroenterol Clin Biol. 2008;32:1064–74. doi: 10.1016/j.gcb.2008.04.030.CrossRefPubMed Laclotte C, Oussalah A, Rey P, Bensenane M, Pluvinage N, Chevaux JB, et al. Helminths and inflammatory bowel diseases. Gastroenterol Clin Biol. 2008;32:1064–74. doi: 10.1016/j.gcb.2008.04.030.CrossRefPubMed
13.
go back to reference Sutton TL, Zhao A, Madden KB, Elfrey JE, Tuft BA, Sullivan CA, et al. Antiinflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect Immun. 2008;76:4772–82. doi:10.1128/IAI.00744-07.CrossRefPubMedCentralPubMed Sutton TL, Zhao A, Madden KB, Elfrey JE, Tuft BA, Sullivan CA, et al. Antiinflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect Immun. 2008;76:4772–82. doi:10.1128/IAI.00744-07.CrossRefPubMedCentralPubMed
14.
go back to reference Melon A, Wang A, Phan V, McKay DM. Infection with Hymenolepis diminuta is more effective than daily corticosteroids in blocking chemically induced colitis in mice. Biomed Biotechnol. 2009;2010:384523. doi:10.1155/2010/384523. Melon A, Wang A, Phan V, McKay DM. Infection with Hymenolepis diminuta is more effective than daily corticosteroids in blocking chemically induced colitis in mice. Biomed Biotechnol. 2009;2010:384523. doi:10.1155/2010/384523.
15.
go back to reference Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun. 2002;70:5931–7.CrossRefPubMedCentralPubMed Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, et al. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun. 2002;70:5931–7.CrossRefPubMedCentralPubMed
16.
go back to reference Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF, Weinstock JV. Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol. 2004;34:2690–8.CrossRefPubMed Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF, Weinstock JV. Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol. 2004;34:2690–8.CrossRefPubMed
17.
go back to reference Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban Jr JF, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol-Gastrointest Liver Physiol. 2003;284:385–91.CrossRef Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban Jr JF, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol-Gastrointest Liver Physiol. 2003;284:385–91.CrossRef
18.
go back to reference Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, Van Rooijen N, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178:4557–66.CrossRefPubMed Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, Van Rooijen N, et al. Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol. 2007;178:4557–66.CrossRefPubMed
20.
go back to reference Summers RW, Elliott DE, Urban Jr JF, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterol. 2005;128:825–32.CrossRef Summers RW, Elliott DE, Urban Jr JF, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterol. 2005;128:825–32.CrossRef
21.
go back to reference Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev. 2014;20(1):CD009400. doi:10.1002/14651858. Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database Syst Rev. 2014;20(1):CD009400. doi:10.1002/14651858.
22.
go back to reference Touil-boukoffa C, Sancëau J, Tayebi B, Wietzerbin J. Relationship among circulating interferon, tumor necrosis factor-α, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis. J Interferon Cytokine Res. 1997;17:211–7.CrossRefPubMed Touil-boukoffa C, Sancëau J, Tayebi B, Wietzerbin J. Relationship among circulating interferon, tumor necrosis factor-α, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis. J Interferon Cytokine Res. 1997;17:211–7.CrossRefPubMed
23.
go back to reference Diaz A, Casaravilla C, Irigoın F, Lin G, Previato J, Fernando F. Understanding the laminated layer of larval Echinococcus I: structure. Trends Parasitol. 2011;27:204–13. doi:10.1016/j.pt.2010.12.012.CrossRefPubMed Diaz A, Casaravilla C, Irigoın F, Lin G, Previato J, Fernando F. Understanding the laminated layer of larval Echinococcus I: structure. Trends Parasitol. 2011;27:204–13. doi:10.1016/j.pt.2010.12.012.CrossRefPubMed
24.
go back to reference Steers NJR, Rogan MT, Heath S. In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production. Parasite Immunol. 2001;23:411–7.CrossRefPubMed Steers NJR, Rogan MT, Heath S. In-vitro susceptibility of hydatid cysts of Echinococcus granulosus to nitric oxide and the effect of the laminated layer on nitric oxide production. Parasite Immunol. 2001;23:411–7.CrossRefPubMed
25.
go back to reference Andrade MA, Siles-Lucas M, Espinoza E, Arellano JLP, Gottstein B, Muro A. Echinococcus multilocularis laminated-layer components and the E14t 14-3-3 recombinant protein decrease NO production by activated rat macrophages in vitro. Nitric Oxide. 2004;10:150–5.CrossRefPubMed Andrade MA, Siles-Lucas M, Espinoza E, Arellano JLP, Gottstein B, Muro A. Echinococcus multilocularis laminated-layer components and the E14t 14-3-3 recombinant protein decrease NO production by activated rat macrophages in vitro. Nitric Oxide. 2004;10:150–5.CrossRefPubMed
26.
go back to reference Siracusano A, Delunardo F, Teggi A, Ortona E. Host-parasite relationship in cystic echinococcosis: an evolving story. Clin Dev Immunol. 2011;2012:639362. doi:10.1155/2012/639362.PubMedCentralPubMed Siracusano A, Delunardo F, Teggi A, Ortona E. Host-parasite relationship in cystic echinococcosis: an evolving story. Clin Dev Immunol. 2011;2012:639362. doi:10.1155/2012/639362.PubMedCentralPubMed
27.
go back to reference Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya RA. Novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterol. 1990;98:694–702. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya RA. Novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterol. 1990;98:694–702.
28.
go back to reference Cooper HS, Murthy SN, Shah RS, Sedergran SJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–49.PubMed Cooper HS, Murthy SN, Shah RS, Sedergran SJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69:238–49.PubMed
29.
go back to reference Messaoudene D, Belguendouz H, Ahmedi ML, Benabdekader T, Otmani F, Terahi M, et al. Ex vivo effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behçet's disease. J inflamm (Lond). 2011;21:35. doi:10.1186/1476-9255-8-35.CrossRef Messaoudene D, Belguendouz H, Ahmedi ML, Benabdekader T, Otmani F, Terahi M, et al. Ex vivo effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behçet's disease. J inflamm (Lond). 2011;21:35. doi:10.1186/1476-9255-8-35.CrossRef
30.
go back to reference Siegmund B, Fantuzzi G, Rieder F, Gamboni-Robertson F, Lehr HA, Hartmann G, et al. Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-γ and TNF-α production. Am J Physiol Regul Integr Comp Physiol. 2001;281:1264–73. Siegmund B, Fantuzzi G, Rieder F, Gamboni-Robertson F, Lehr HA, Hartmann G, et al. Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-γ and TNF-α production. Am J Physiol Regul Integr Comp Physiol. 2001;281:1264–73.
31.
go back to reference Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114:385–91.CrossRefPubMedCentralPubMed Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114:385–91.CrossRefPubMedCentralPubMed
32.
go back to reference Obermeier F, Kojouharoff G, Hans W, Scholmerich J, Gross V, Falk W. Interferongamma (IFN-γ)-and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol. 1999;116:238–45.CrossRefPubMedCentralPubMed Obermeier F, Kojouharoff G, Hans W, Scholmerich J, Gross V, Falk W. Interferongamma (IFN-γ)-and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol. 1999;116:238–45.CrossRefPubMedCentralPubMed
33.
go back to reference Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Ackerman Z, Podolsky DK. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Gut. 1995;36:718–23.CrossRefPubMedCentralPubMed Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Ackerman Z, Podolsky DK. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Gut. 1995;36:718–23.CrossRefPubMedCentralPubMed
34.
go back to reference Saura M, Zaragoza C, Clare B, McMillan A, Lowenstein CJ. Interaction of interferon regulatory factor-1 and nuclear factor kB during activation of inducible nitric oxide synthase transcription. J Mol Biol. 1999;289:459–71.CrossRefPubMed Saura M, Zaragoza C, Clare B, McMillan A, Lowenstein CJ. Interaction of interferon regulatory factor-1 and nuclear factor kB during activation of inducible nitric oxide synthase transcription. J Mol Biol. 1999;289:459–71.CrossRefPubMed
35.
go back to reference Cheshire JL, Baldwin AS. Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation. Mol Cell Biol. 1997;17:6746–54.PubMedCentralPubMed Cheshire JL, Baldwin AS. Synergistic activation of NF-kappaB by tumor necrosis factor alpha and gamma interferon via enhanced I kappaB alpha degradation and de novo I kappaBbeta degradation. Mol Cell Biol. 1997;17:6746–54.PubMedCentralPubMed
36.
go back to reference Schottelius AJG, Baldwin Jr AS. A role for transcription factor NF-kB in intestinal inflammation. Int J Colorectal Dis. 1999;14:18–28.CrossRefPubMed Schottelius AJG, Baldwin Jr AS. A role for transcription factor NF-kB in intestinal inflammation. Int J Colorectal Dis. 1999;14:18–28.CrossRefPubMed
37.
go back to reference Díaz A, Casaravilla C, Allen JE, Sim RB, Ferreira AM. Understanding the laminated layer of larval Echinococcus II: immunology. Trends Parasitol. 2011;27:264–73. doi:10.1016/j.pt.2011.01.008.CrossRefPubMed Díaz A, Casaravilla C, Allen JE, Sim RB, Ferreira AM. Understanding the laminated layer of larval Echinococcus II: immunology. Trends Parasitol. 2011;27:264–73. doi:10.1016/j.pt.2011.01.008.CrossRefPubMed
38.
go back to reference Maizels RM, Balic A, Gomez‐Escobar N, Nair M, Taylor MD, Allen JE. Helminth parasites–masters of regulation. Immunol Rev. 2004;201:89–116.CrossRefPubMed Maizels RM, Balic A, Gomez‐Escobar N, Nair M, Taylor MD, Allen JE. Helminth parasites–masters of regulation. Immunol Rev. 2004;201:89–116.CrossRefPubMed
Metadata
Title
Crude extract of hydatid laminated layer from Echinococcus granulosus cyst attenuates mucosal intestinal damage and inflammatory responses in Dextran Sulfate Sodium induced colitis in mice
Authors
Imene Soufli
Ryma Toumi
Hayet Rafa
Manel Amri
Moussa Labsi
Lila Khelifi
Ferdinando Nicoletti
Chafia Touil-Boukoffa
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2015
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-015-0063-6

Other articles of this Issue 1/2015

Journal of Inflammation 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.