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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 8/2010

01-08-2010 | Original Article

A Model for Chronic Mucosal Inflammation in IBD and Periodontitis

Authors: Helieh S. Oz, Theresa Chen, Jeffrey L. Ebersole

Published in: Digestive Diseases and Sciences | Issue 8/2010

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Abstract

Background

Chronic inflammation of mucosal surfaces is an aberrant immune response to luminal bacteria and generates an array of oxygen radicals leading to tissue destruction and loss of function, as noted in IBD and periodontitis. We hypothesized that mucosal injury after “oral delivery” of dextran sulfate sodium (DSS) or TNBS for an extended period of 18 weeks is reflected by chronic inflammatory responses in a time-dependent fashion.

Methods

Dextran sulfate sodium was administered in the diet biweekly; TNBS or sham controls was administered orally twice a week. Additional groups received TNBS or sham injections into gingival tissue.

Results

Animals tolerated oral applications with no severe clinical symptoms. The DSS-group developed diarrhea during the period of administration, and returned to normal during DSS abstinence. The TNBS-group developed no systemic clinical symptoms. Splenic length and weight increased in the DSS-group in a time-dependent fashion (P < 0.01) and remained normal in the TNBS-group. Colons from the DSS-group were significantly shortened (P < 0.001) and colonic weight increased compared with controls or the TNBS-group (P < 0.05). The DSS-group developed extensive dilation of the stomach wall, ileum, and megacolon, with abdominal fat deposits. In addition, the DSS-group showed dysregulated hepatic concentrations of antioxidants (i.e. cysteine, GSH, SAMe) in a time-dependent manner that correlated with a significance increase in alveolar bone resorption. Localized TNBS-mucosal delivery caused severe inflammation, granuloma formation, and rapid bone resorption.

Conclusions

This model of mucosal stimulation eliciting chronic inflammatory responses in the gut and oral cavity mimics aspects of IBD and periodontal disease progression in patients.
Literature
1.
Oz HS, Ebersole JL. Application of prodrugs to inflammatory diseases of the gut. Molecules. 2008;13:452–474. (review).CrossRefPubMed
2.
Neuman MG. Immune dysfunction in inflammatory bowel disease. Transl Res. 2007;149:173–186. (review).CrossRefPubMed
3.
Byme FR, Viney JL. Mouse models of inflammatory bowel disease. Curr Opin Drug Discov Devel. 2006;9:207–217. (review).
4.
Chapple IL. Reactive oxygen species and antioxidants in inflammatory diseases. J Clin Periodontol. 1997;24:287–296.CrossRefPubMed
5.
Kesavalu L, Bakthavatchalu V, Rahman MM, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol. 2007;22:232–239.CrossRefPubMed
6.
Chapple IL, Brock G, Eftimiadi C, Mathews JB. Glutathione in gingival crevicular fluid and its relation to local antioxidant capacity in periodontal health and disease. J Clin Pathol Mol Pathol. 2002;55:367–373.CrossRef
7.
Waddington RJ, Moseley R, Embery G. Reactive oxygen species: A potential role in the pathogenesis of periodontal diseases. Oral Dis. 2000;6:138–151.PubMedCrossRef
8.
Marangon K, Devaraj S, Tirosh O, Packer L, Jialal I. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic Biol Med. 1999;27:1114–1121.CrossRefPubMed
9.
Kim HJ, Chang EJ, Kim HM, et al. Antioxidant alpha-lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappaB DNA binding and prevents in vivo bone resorption induced by receptor activator of nuclear factor-kappaB ligand and tumor necrosis factor-alpha. Free Radic Biol Med. 2006;40:1483–1493.CrossRefPubMed
10.
Holt SC, Ebersole JL. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: The “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000. 2005;38:72–122.CrossRefPubMed
11.
Enwonwu CO. Cellular and molecular effects of malnutrition and their relevance to periodontal diseases. J Clin Periodontol. 1994;21:643–657.CrossRefPubMed
12.
Enwonwu CO. Interface of malnutrition and periodontal diseases. Am J Clin Nutr. 1995;61:430S–436S.PubMed
13.
Kawashi Y, Jaccard F, Cimasoni G. Sulcular polymorphonuclear leukocytes and gingival exudates during experimental gingivitis in man. J Periodontol Res. 1980;15:151–158.CrossRef
14.
Gustafsson A, Asman B. Increased release of free oxygen radicals from peripheral neutrophils in adult periodontitis after Fc delta-receptor stimulation. J Clin Periodontol. 1996;23:38–44.CrossRefPubMed
15.
16.
Makins R, Ballinger A. Gastrointestinal side effects of drugs. Expert Opin Drug Saf. 2003;2:421–429. (review).CrossRefPubMed
17.
Brito F, de Barros FC, Zaltman C, et al. Prevalence of periodontitis and DMFT index in patients with Crohn’s disease and ulcerative colitis. J Clin Periodontol. 2008;35:555–560.CrossRefPubMed
18.
Galbraith SS, Drolet BA, Kugathasan S, Paller AS, Esterly NB. Asymptomatic inflammatory bowel disease presenting with mucocutaneous findings. Pediatrics. 2005;116:e439–e444.CrossRefPubMed
19.
Ojha J, Cohen DM, Islam NM, Stewart CM, Katz J, Bhattacharyya I. Gingival involvement in Crohn disease. J Am Dent Assoc. 2007;138:1574–1581.PubMed
20.
Grössner-Schreiber B, Fetter T, Hedderich J, Kocher T, Schreiber S, Jepsen S. Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: A case–control study. J Clin Periodontol. 2006;33:478–484.CrossRefPubMed
21.
Mdinaridze GN, Rumiantsev VG, Maksimovskiĭ IM, Iurkov MI. State of the mouth cavity in patients with inflammatory intestinal diseases]. Eksp Klin Gastroenterol. 2006;4:17–21, 114.PubMed
22.
Rezaie A, Ghorbani F, Eshghtork A, et al. Alterations in salivary antioxidants, nitric oxide, and transforming growth factor-beta 1 in relation to disease activity in Crohn’s disease patients. Ann N Y Acad Sci. 2006;1091:110–122.CrossRefPubMed
23.
Heitz-Mayfield LJ, Schätzle M, Löe H, et al. Clinical course of chronic periodontitis. II. Incidence, characteristics and time of occurrence of the initial periodontal lesion. J Clin Periodontol. 2003;10:902–908.CrossRef
24.
Oz HS, Chen T, de Villiers W, McClain C. Metallothionein overexpression does not protect against inflammatory bowel disease in a DSS murine colitis model. Med Sci Monit. 2005;11:BR69–BR73.PubMed
25.
Oz HS, Chen TS, McClain CJ, de Villiers WJ. Antioxidants a novel therapy in a murine model of colitis. J Nutri Biochem. 2005;16:297–304.CrossRef
26.
Oz HS, Chen T, Nagasawa H. Comparative efficacies of two cysteine prodrugs and a glutathione delivery agent in a colitis model. Transl Res. 2007;150:122–129.CrossRefPubMed
27.
Ardite E, Sans M, Panes J, Romero FJ, Pique JM, Fernandez-Checa JC. Replenishment of glutathione levels improves mucosal function in experimental acute colitis. Lab Invest. 2000;80:735–744.PubMed
28.
Oz HS, Zhong J, de Villiers W. Osteopontin ablation protects against progression of acute and chronic stages of TNBS-induced colitis. Gastroenterol Supl. 2008;134:A-525, T1296.
29.
Garcia-Lafhente A, Antolin M, Guarner F, et al. Incrimination of anaerobic bacteria in the induction of experimental colitis. Am J Physiol. 1997;272:G10–G15.
30.
Axelsson LG, Landström E, Bylund-Fellenius AC. Experimental colitis induced by dextran sulfate sodium in mice: Beneficial effects of sulfasalazine and olsalazine. Aliment Pharmacol Ther. 1998;12:925–934.CrossRefPubMed
31.
Oz HS, Ebersole JL. A novel murine model for chronic inflammatory alveolar bone loss. J Periodont Res. (in press).
32.
Brandtzaeg P. Inflammatory bowel disease: Clinics and pathology. Do inflammatory bowel disease and periodontal disease have similar immunopathogeneses? Acta Odontol Scand. 2001;59:235–243.CrossRefPubMed
33.
Colella G, Riegler G, Lanza A, Tartaro GP, Russo MI, Tartaglione M. Changes in the mouth mucosa in patients with chronic inflammatory intestinal diseases. Minerva Stomatol. 1999;48:367–371.PubMed
34.
Flemmig TF, Shanahan F, Miyasaki KT. Prevalence and severity of periodontal disease in patients with inflammatory bowel disease. J Clin Periodontol. 1991;18:690–697.CrossRefPubMed
35.
Girlich C, Bogenrieder T, Palitzsch KD, Schölmerich J, Lock G. Orofacial granulomatosis as initial manifestation of Crohn’s disease: A report of two cases. Eur J Gastroenterol Hepatol. 2002;14:873–876.CrossRefPubMed
36.
Sigusch BW. Periodontitis as manifestation of Crohn’s disease in primary dentition: A case report. J Dent Child (Chic). 2004;71:193–196.
37.
Sculley DV, Langley-Evans SC. Salivary antioxidants and periodontal disease. Proc Nutr Soc. 2002;61:137–143.CrossRefPubMed
38.
Bretz WA, Weyant RJ, Corby PM, et al. Systemic inflammatory markers, periodontal diseases, and periodontal infections in an elderly population. J Am Geriatr Soc. 2005;53:1532–1537.CrossRefPubMed
39.
Ebersole JL, Taubman MA. The protective nature of host responses in periodontal diseases. Periodontol 2000. 1994;5:112–141.CrossRefPubMed
40.
Garlet GP, Martins W Jr, Fonseca BA, Ferreira BR, Silva JS. Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. J Clin Periodontol. 2004;31:671–679.CrossRefPubMed
41.
Sharma CG, Pradeep AR. Gingival crevicular fluid osteopontin levels in periodontal health and disease. J Periodontol. 2006;77:1674–1680.CrossRefPubMed
42.
Mishima R, Takeshima E, Sawi K, et al. High plasma opsteopontin levels in patients with inflammatory bowel disease. J Clinic Gasteroentrol. 2007;41:162–172.
43.
Zhong J, Eckhart E, Oz HS, Bruemmer D, de Villiers W. Osteopontin deficiency protects mice from DSS-induced colitis. Inflamm Bowel Dis. 2006;12:790–796.CrossRefPubMed
44.
Pizarro TT, Cominelli F. Cytokine therapy for Crohn’s disease: Advances in translational research. Annu Rev Med. 2007;58:433–444.CrossRefPubMed
45.
Schwartz L, Abolhassani M, Pooya M, et al. Hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2A. Am J Physiol Gastrointest Liver Physiol. 2008;295:G934–G941.CrossRefPubMed
46.
Oz HS IMH, Chen T, de Villiers W, McClain C. Glutathione enhancing agents protect against Steatohepatitis in a model. J Biochem Mol Toxicol. 2006;20:39–47.CrossRefPubMed
47.
Oz HS, McClain CJ, Nagasawa HT, Ray MB, de Villiers WJ, Chen TS. Diverse antioxidants protect against acetaminophen hepatotoxicity. J Biochem Mol Toxicol. 2004;18(6):361–368.CrossRefPubMed
48.
Ko K, Yang H, Noureddin M, et al. Changes in S-adenosylmethionine and GSH homeostasis during endotoxemia in mice. Lab Invest. 2008;88:1121–1129.CrossRefPubMed
Metadata
Title
A Model for Chronic Mucosal Inflammation in IBD and Periodontitis
Authors
Helieh S. Oz
Theresa Chen
Jeffrey L. Ebersole
Publication date
01-08-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 8/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-1031-x

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