↑ IFN- , TNF
RT PCR: real-time PCR; MSI: multiplex sandwich immunoassay; IFN- γ : interferone gama; IL: interleukine; GM-CSF: granulocyte-macrophage colony-stimulating factor; IP-10: interferon-inducible protein; KC: keratinocyte-derived chemokine; MCP-1: monocyte chemoattractant protein; MIG: monokine induced by IFN- γ ; MIP-1 α : macrophage inflammatory protein; TNF- α : tumor necrosis factor alpha.
These inflammatory mediators not only play a role in the pathogenesis of DSS-induced colitis but are important as intervention targets against colitis as excellently described by Kawada et al. [ 52 ]. Cytokine profile in DSS colitis correlates with clinical and histological parameters as well as barrier properties. Different expression depending on strain and phase of colitis provides this model as a useful tool to dissect the role of these cytokines in the induction of inflammation and recovery from it.
Recently comprehensive study of mucosal and systemic immune responses in C57BL/6OlaHsd mice exposed to 3% DSS for 6 days has been performed using immunofluorescent staining and flow cytometry analyses. It has been shown that adaptive immune responses in this mouse strain are induced during both acute and chronic phase of colitis in all organs tested, that are, colon, spleen, and mesenteric lymph nodes as early as day 1 of DSS treatment until the end (i.e., day 25) [ 23 ]. Interplay of neutrophils, dendritic cells, macrophages, and T and B cells among spleen, mesenteric lymph nodes, and colon in DSS-treated C57BL/6OlaHsd mice in temporal fashion is schematically represented in Figure 8 .
Schematic representation of mucosal (colon) and systemic (spleen, MLN) immune responses in C57BL/6OlaHsd mice exposed to 3% DSS for 6 days followed by water for 19 days. Measurements were made on day 0, 1, 3, 5, 8, 12, and 25 as denoted by numbers. Schematic representation is based on results obtained by Hall et al. [ 23 ]. MLN: mesenteric lymph nodes, N: neutrophils, M: macrophages, DC: dendritic cells, T: T cells, B: B cells.
DSS-induced colitis is nowadays frequently used in genetically engineered mice (GEM), to study basic immunologic mechanisms of IBD and to elucidate the role of particular deleted ( −/− ) or inserted (Tg) gene in the pathogenesis of the colitis.
Toll-like receptors (TLR) are critical receptors and signal transducers for structurally conserved pathogen-associated molecular patterns of bacterial cell components (such as lipopolysaccharide) that provoke innate immune responses by stimulating macrophages/dendritic cells to produce proinflammatory cytokines. It has been shown that mice deficient for different TLR (TLR2, TLR4) or other molecules, which are implicated in signaling via TLR such as myeloid differential protein (MyD88), are very susceptible to DSS colitis, indicating important protective role of these molecules in colitis [ 33 , 53 – 55 ]. Overproduction of IL-18 or deletion of TNF- α has been shown to exacerbate DSS colitis [ 51 , 56 ]. On the other hand mice deficient for IL-15 showed reduced susceptibility to DSS colitis [ 58 ]. Mice deficit for IL-12 developed mild DSS colitis, while mice deficit for IL-18 developed severe colitis associated with high lethality [ 69 ]. Deletion of suppressor of cytokine signaling-1 (SOCS-1), which is a negative feedback molecule for cytokine signaling, increased susceptibility to DSS colitis, suggesting that SOCS-1 plays preventive role in the development of DSS-induced colitis in mice by inhibiting IFN- γ /STAT1 signaling [ 61 ]. Interferon regulatory factor-1 (IRF-1) is a transcription factor stimulated by IFN- γ and TNF- α that binds to the promoter region of inflammation-related genes, such as IFN- α , IFN- β , and iNOS. It is expressed in lymphocytes, monocytes, and a wide variety of other cell types, including enterocytes. Mice lacking IRF-1 transcription factor developed significantly increased DSS-induced colonic dysplasia [ 62 ]. Tryptophan hydroxylase-1 (TPH1) catalyzes the rate-limiting step in the synthesis of 5-hydroxytryptamine (5-HT) from tryptophan. It is an important enteric mucosal signaling molecule influencing gut physiology (motor and secretory function) following inflammation and is considered important in maintaining intestinal homeostasis. However, mice lacking TPH1 had significantly reduced susceptibility to DSS colitis [ 65 ].
Taken together, GEM treated with DSS are valuable model to test different molecules, which are involved in the mediation of inflammation such as cytokines (IL-12, IL-15, IL-18, TNF- α ), nitric oxides (iNOS, eNOS, and nNOS), complement system activation products or other molecules involved in signaling of inflammation (SOCS-1, IRF-1), to further identify bacterial factors involved in maintaining intestinal homeostasis (TLR, MyD88), to investigate the role of particular factor when totally deleted or deleted only in particular types of cells such as intestinal, (PPAR γ ΔIEpC ; Vhl ΔF/F ; Hif-1 α ΔF/F ; Arnt ΔF/F ) or CD4+ T cells (PPAR γ ΔCD4+ ) and to test therapeutic interventions based upon inhibition of particular gene expression strategies (TPH1, APN, and MRP1). In the Table 4 susceptibility to DSS-induced colitis in mice deficient for a particular gene is shown. Mouse background, gender, microbiological state, molecular weight of DSS, and DSS treatment, factors that importantly affect DSS colitis and need to be taken into account in designing investigation or evaluating results, are also stated.
DSS-induced model is simple to induce and not expensive, which makes it one of the most commonly used model of IBD to study various aspects of IBD such as pathogenesis, genetic predisposition to IBD, immune mechanisms, and role of microflora in the pathogenesis of IBD as well as bowel malignancy secondary to IBD. As demonstrated above, various factors may affect susceptibility to DSS and modify results. Representative examples of how important can be all mentioned details are studies where two groups of researchers investigated the role of adiponectine in DSS colitis. Both groups used in their studies the same mice model (mice with APN deletion) exposed to DSS treatment. They observed quite opposite results [ 66 , 67 ]. It is thus advisable to state and describe all details and conditions that may affect the DSS susceptibility.
This work was in part supported by ARRS (Slovenian Research Agency, Program P3-0054).
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The use of oral and intravenous cyclosporin represents a significant advance in the therapy of refractory inflammatory bowel diseases (IBD). However, oral administration of cyclosporin is fraught with improper delivery of cyclosporin to the colon for its topical action. Because of unpredictable metabolism by cytochrome P-450 IIIA, the targeted blood level for systemic effect is not reached at low doses. Furthermore, the doses that have been used for therapy of IBD have been shown to induce several adverse side effects. Thus, an alternate method of delivering cyclosporin to the colon is desirable. In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000–40,000 mol wt) for five or seven days, respectively. Therapy was advocated prophylactically, prophylaxis plus therapy and therapeutically during the acute and chronic phase of the disease and therapeutically during the chronic phase of the disease. Intracolonic cyclosporin given prophylactically showed adverse effects by increasing the damage to the colonic mucosa. However, intracolonic cyclosporin given therapeutically in 2.5, 5, and 10 mg/kg after the induction of colitis resulted in dramatic responses in terms of reducing the disease activity and histologic scores, corroborated by complete histological resolution compared to oral cyclosporin given at identical doses. Intracolonic cyclosporin (5 mg/kg) was also very effective in reducing the chronic inflammation. The results of this study highlight the application of this animal model for therapeutic research. Furthermore, cyclosporin administered as an enema provides a new stratagem for the therapy of IBD because of its rapid onset of action at very low doses without the risk inherent in oral or systemic administration.
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Riddell RH: Pathology of idiopathic inflammatory bowel diseases. In Inflammatory Bowel Diseases. JB Kirsner RG Shorter (ed). Philadelphia, Lea and Febiger, 1988, pp 329–350
Google Scholar
Lauritsen K: Drug treatment and formation of eicosanoids in patients with chronic inflammatory bowel diseases. Danish Med Bull 36:378–393, 1989
Sutherland L, Singelton F, Sessions F, Hanauer S, Karwitt E, Ranking G, Summers R, Mekhjian H, Greenberger N, Kelly M, Levine L, Thomson A, Alpert E: Double blind placebo controlled trial of metronidazole in Crohn's disease. Gut 18:1071–1075, 1991
Present DH: 6-Mercaptopurine and other immunosuppressive agents in the treatment of Crohn's disease and ulcerative colitis. Gastroenterol Clin North Am 18:57–71, 1989
Stange EF, Fleig WE, Rekhlaw E, Ditschuneit H: Cyclosporin A treatment in inflammatory bowel diseases. Dig Dis Sci 34:1387–1392, 1989
Lichteger S, Present DH: Preliminary report: Cyclosporin in treatment of severe active ulcerative colitis. Lancet 336(8706):16–19, 1990
Porro GB, Panza E, Petrillo M: Cyclosporin A in acute ulcerative colitis. Lancet 2:1277–1278, 1984
Lobo AJ, Juby LD, Foster RN, Rothwell J, Smith AH, Axon ATR: Oral cyclosporin and renal function in Crohn's disease. Gut 30:A1480, 1989
Watkins PB: The role of cytochrome P-450 IIIA in cyclosporin metabolism. J Am Acad Dermatol 23:1309–1311, 1990
Sandborn WJ, Strong RM, Forland SC, Chase RL, Cutter RE: The pharmacokinetics and colonic tissue concentrations after IV, oral and enema administration. J Clin Pharmacol 31:76–80, 1991
Brynskov J, Freund L, Thomsen OO, Anderson CB, Rasmussen SN, Binder V: Treatment of refractory ulcerative colitis with cyclosporin enemas. Lancet 1:721–722, 1989
Sandborn WJ, Tremaine WJ, Schroeder KW, Batts KP, Lawson GM: Cyclosporine (CYA) enemas for treatment-resistant, ulcerative proctosignoiditis (UPS). Gastroenterology 102:A690, 1992
Winter T, Dalton HR, Merrett MN, Campbell A, Jewell DP: Cyclosporin A retention enemas in refractory distal ulcerative colitis: An open trial. Gastroenterology 102:A947, 1992
Ranzi T, Campanini MC, Velio P, Quarto di Palo F, Bianchi P: Treatment of chronic proctosigmoiditis with cyclosporin enemas. Lancet 2:97, 1989
Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R: Novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702, 1990
Cooper HS, Murthy SNS, Shah RS, Sedergran DJ: Clinicopathological study of dextran sulfate sodium experimental murine colitis. Lab Invest (submitted)
Dunnet CW: Multiple comparison tests. Biometrica 26:139–141, 1970
Newman D: The distribution of range in sample from a normal population expressed in terms of independent estimate of standard deviation. Biometrica 31:20–30, 1939
Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803, 1989
Fitzpatric LR, Bostwick JS, Renzetti M, Pendleton RG, Dektor DL: Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat. Agents Actions 30:399–411, 1990
Azad Khan AK, Piris J, Truelove SC: An experiment to determine the actual therapeutic moiety of sulphasalazine. Lancet 2:892–895, 1977
Meyers S, Sachar DB, Present DH, Janowitz HD: Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine. A prospective, randomized placebo-controlled, double blind, dose ranging clinical trial. Gastroenterology 93:1255–1262, 1987
Robinson MG: New oral salicylates in the therapy of chronic idiopathic inflammatory bowel disease. Gastroenterol Clin North Am 18:43–49, 1989
Sutherland LR, Martin F, Greer S, Robinson MG, Greenberger N, Sarbid F, Martin T, Sparr J, Prokipchuk ED, Borgen L: 5-Aminosalicylic acid enemas in the treatment of distal ulcerative colitis, proctosigmoiditis and proctitis. Gastroenterology 92:1844–1848, 1987
Kolars JC, Duell EA, Schmiedlin-Ren P, Ellis CN, Voorhees JJ, Watkins PB: Cyclosporin metabolism by cytochrome P-450 IIIA in rat enterocytes: Another determinant of oral bioavailability. Gastroenterology 98:A192, 1990
Kronke M, Leonard WJ, Deeper JM, Green WC: Sequential expression of genes involved in human lymphocyte growth and differentiation. J Exp Med 161:1593–1598, 1985
Wagner H: Cyclosporin A: Mechanism action. Transplant Proc 15:523–526, 1983
Kubes P, Hunter J, Granger DN: Effects of cyclosporin A and FK 506 on ischemia/reperfusion-induced neutrophil infiltration in the cat. Dig Dis Sci 36:1469–1472, 1991
Thomson AW, Moon DK, Geczy CL, Nelson DS: Modification of delayed-hypersensitivity reactions to ovalbumin in cyclosporin A-treated guinea pigs. Immunology 48:301–308, 1983
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Krancer Center for Inflammatory Bowel Disease Research, Division of Gastroenterology, Department of Medicine, Hahnemann University, Broad and Vine Streets, Mail Stop 131, 19102-1192, Philadelphia, Pennsylvania
S. N. S. Murthy PhD, Harry S. Cooper MD, Helen Shim MD, Rupal S. Shah BS, Samih A. Ibrahim MS & Deborah J. Sedergran MT (ASCP)
Department of Pathology and Laboratory Medicine, Hahnemann University, Broad and Vine Streets, 19102-1192, Philadelphia, Pennsylvania
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Murthy, S.N.S., Cooper, H.S., Shim, H. et al. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Digest Dis Sci 38 , 1722–1734 (1993). https://doi.org/10.1007/BF01303184
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Received : 02 March 1992
Revised : 14 October 1992
Accepted : 20 October 1992
Issue Date : September 1993
DOI : https://doi.org/10.1007/BF01303184
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Clinicopathologic study of dextran sulfate sodium experimental murine colitis..
BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. EXPERIMENTAL DESIGN: Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. RESULTS: Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. CONCLUSIONS: The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.
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Animal models of inflammatory bowel disease (IBD) are valuable tools for investigating the factors involved in IBD pathogenesis and evaluating new therapeutic options. The dextran sodium sulfate (DSS)-induced model of colitis is arguably the most widely used animal model for studying the pathogenesis of and potential treatments for ulcerative colitis (UC), which is a primary form of IBD. This model offers several advantages as a research tool: it is highly reproducible, relatively easy to generate and maintain, and mimics many critical features of human IBD. Recently, it has also been used to study the role of gut microbiota in the development and progression of IBD and to investigate the effects of other factors, such as diet and genetics, on colitis severity. However, although DSS-induced colitis is the most popular and flexible model for preclinical IBD research, it is not an exact replica of human colitis, and some results obtained from this model cannot be directly applied to humans. This review aims to comprehensively discuss different factors that may be involved in the pathogenesis of DSS-induced colitis and the issues that should be considered when using this model for translational purposes.
Keywords: chemically induced colitis model; pathogenesis mechanism of action; preclinical research; sulfated glucan; ulcerative colitis.
This review discusses different factors that may be involved in the pathogenesis of DSS-induced colitis and the issues that should be considered when using this model for translational purposes.
Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation 2024.
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COMMENTS
The hypothesis that appendicular lymphoid tissue, but not the spleen, contributes to the development of colitis is supported by experimentally assessing the importance of secondary lymphoid tissues in inducing colitis in mice. Dysplasia and cancer in the dextran sulfate sodium mouse colitis model.
Background: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. Experimental design: Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS ...
Clinicopathologic study of dextran sulfate sodium experimental acute colitis January 1998 The Japanese Journal of Pharmacology 76:297 DOI: 10.1016/S0021-5198 (19)41298-5 License CC BY-NC-ND 4.0 ...
Background: Murine models are essential tools to understand IBD pathogenesis. Among different types of chemically induced colitis models, the dextran sulfate sodium (DSS)-induced colitis model is the most common model of IBD, due to its simplicity.
The most widely used experimental model employs dextran sodium sulfate (DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity, simplicity, reproducibility and controllability.
Clinicopathologic study of dextran sulfate sodium experimental murine colitis. H S Cooper, S N Murthy, R S Shah, D J Sedergran Laboratory Investigation; a Journal of Technical Methods and Pathology 1993 August BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and ...
Inflammation of the gastrointestinal tract contributes to the development of inflammatory bowel disease (IBD). Human IBD is modeled by administering dextran sulfate sodium (DSS) to mice. In humans ...
A laboratory investigation article from 1993 that compares the clinical and pathologic features of acute and chronic colitis induced by dextran sulfate sodium in mice. The article provides keywords, abstract, authors, source, publication details and classification information.
In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000-40,000 mol wt) for five or seven days, respectively.
A study of the clinical and histopathologic features of acute and chronic colitis induced by oral DSS in mice. The earliest histologic change was crypt loss without inflammation, suggesting a primary epithelial injury and a secondary inflammatory response.
Abstract Dextran sulfate sodium (DSS)-induced murine colitis represents an experimental model for human inflammatory bowel disease. The aim of this study was to screen various inbred strains of mice for genetically determined differences in susceptibility to DSS-induced colitis.
Experimental study showed that Danshen had protective effect on acute colitis induced by dextran sulfate sodium (DSS) [11]. Cryptotanshinone (CTS) is one of the main active components of Danshen, with anti-inflammation, anti-oxidation, anticancer and other pharmacological activities [12], [13], [14], [15].
The dextran sulphate sodium model of colitis has demonstrated several correlations with human inflammatory bowel disease and is deemed suitable for investigating pathogenesis, therapeutic options and the dysplasia-adenocarcinoma sequence of inflammatory bowel disease. It is widely applicable to mice, rats, hamsters and guinea pigs.
Background We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis.
In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines ...
The mouse model of dextran sulfate sodium (DSS) -induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the ...
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Both dextran sulphate sodium (DSS) and trinitrobenzene sulfonic acid (TNBS-) induced colitis are well-established animal models of mucosal inflammation that have been used for over 2 decades in the study of IBD pathogenesis and preclinical studies [ 6 - 8 ].
In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000-40,000 mol wt) for five or seven days, respectively.
BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. EXPERIMENTAL DESIGN: Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS ...
KW-5617 nay be a useful drug for the treatment of diarrhea in terns of less side effect concerning constipation. P-659 Clinicopathologic study of dextran sulfate sodium experimental acute colitis.
The dextran sodium sulfate (DSS)-induced model of colitis is arguably the most widely used animal model for studying the pathogenesis of and potential treatments for ulcerative colitis (UC), which is a primary form of IBD. This model offers several advantages as a research tool: it is highly reproducible, relatively easy to generate and ...