The Severity of Dextran Sodium Sulfate-Induced Colitis Can Differ Between Dextran Sodium Sulfate Preparations of the Same Molecular Weight Range

Bamba, Shigeki; Andoh, Akira; Ban, Hiromitsu; Imaeda, Hirotsugu; Aomatsu, Tomoki; Kobori, Ayako; Mochizuki, Yosuke; Shioya, Makoto; Nishimura, Takashi; Inatomi, Osamu; Sasaki, Makoto; Saitoh, Yasuharu; Tsujikawa, Tomoyuki; Araki, Yoshio; Fujiyama, Yoshihide

doi:10.1007/s10620-011-1881-x

Cited by 18 publications

(20 citation statements)

References 23 publications

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“…On the other hand, our data suggest that MT deficiency results in disease exacerbation in a mouse model of DSS-induced colitis, and that MTs play a protective role in the development of intestinal inflammation. While considering these results, we noted differences in the manufacture of DSS and vivarium in these studies, and it has been reported that these factors can lead to differences in the severity of DSS-induced colitis (34,35).…”

Section: Discussionmentioning

confidence: 67%

Role of metallothionein in murine experimental colitis

Tsuji

Naito

Takagi

et al. 2013

International Journal of Molecular Medicine

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Abstract. Metallothioneins (MTs) are a family of cysteine-rich low molecular-weight proteins that can act as reactive oxygen species scavengers. Although it is known that the induction of MT expression suppresses various inflammatory disorders, the role of MTs in intestinal inflammation remains unclear. In this study, we investigated the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the MT-I/II genes. Acute colitis was induced by 2% DSS in male MT-I/II double knockout (MT-null) and C57BL/6 (wild-type) mice. The disease activity index (DAI) was determined on a daily basis for each animal, and consisted of a calculated score based on changes in body weight, stool consistency and intestinal bleeding. Histology, colon length, myeloperoxidase (MPO) activity and colonic mRNA expression and the concentration of inflammatory cytokines were evaluated by real-time-PCR and enzyme-linked immunosorbent assay (ELISA). The localization of MTs and macrophages was determined by immunohistological and immunofluorescence staining. To investigate the role of MTs in macrophages, peritoneal macrophages were isolated and their responses to lipopolysaccharide were measured. Following DSS administration, the DAI score increased in a time-dependent manner and was significantly enhanced in the MT-I/II knockout mice. Colonic MPO activity levels and inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17] production increased following DSS administration, and these increases were significantly enhanced in the MT-I/II knockout mice compared with the wild-type mice. MT-positive cells were detected in the lamina propria and submucosal layer by immunohistochemical and immunofluorescence staining, and were mainly co-localized in F4/80-positive macrophages. The production of inflammatory cytokines (TNF-α, IFN-γ and IL-17) from isolated peritoneal macrophages increased following lipopolysaccharide stimulation, and these increases were significantly enhanced in the macrophages obtained from the MT-I/II knockout mice. These data indicate that MTs play an important role in the prevention of colonic mucosal inflammation in a mouse model of DSS-induced colitis, thus suggesting that endogenous MTs play a protective role against intestinal inflammation. IntroductionInflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease are known as refractory and recurrent diseases of the gastrointestinal tract. Although the features of IBDs suggest a number of possible causes, including genetic, infectious and immunological factors, the precise pathogenesis of IBDs remains unknown (1-3). Recent evidence suggests that oxidative stress caused by reactive oxygen species (ROS) is an important factor involved in the onset and development of intestinal inflammation. Furthermore, it has also been demonstrated that disruptions in the antioxidant defense system are involved in the pathophysiology of IBDs (4,5). Therefore, it is important to investigate the oxidative s...

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Section: Discussionmentioning

confidence: 67%

Role of metallothionein in murine experimental colitis

Tsuji

Naito

Takagi

et al. 2013

International Journal of Molecular Medicine

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“…14 Figure 1 displays the acute disease activity index for different experimental groups. A validated index (1 indicating no disease; 4 indicating the most severe disease) of average scores based on the combination of clinical symptoms (body weight, diarrhea, fecal occult blood/prolapse and colon length) was constructed (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Further, a recent investigation indicated that the severity of colitis can differ between similar DSS preparations of the same molecular weight range. 14 This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation. The DSS used in the present investigation was reported to cause the most severe disease and weight loss.…”

Section: Resultsmentioning

confidence: 99%

“…The DSS used in the present investigation was reported to cause the most severe disease and weight loss. 14 …”

Section: Resultsmentioning

confidence: 99%

“…The rapidity of the acute model suggests that adaptive immunity is not pivotal to the development of lesions or crypt erosion in the colonic mucosa. 14 Furthermore, no precise inflammatory mechanisms have been identified that contribute to the genesis of acute lesions. Similar DSS-induced lesions were also observed in the case of severe combined immunodeficient mice, thus ruling out any involvement of B- or T-cells in the pathology.…”

Section: Resultsmentioning

confidence: 99%

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Interventional Effects of Plumbagin on Experimental Ulcerative Colitis in Mice

et al. 2013

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Plumbagin (1) is a naphthoquinone constituent of plants that have been used in traditional systems of medicine since ancient times. In the present study, the role of 1 was examined on the amelioration of ulcerative colitis, an inflammatory bowel disease that is not curable currently. Plumbagin was tested at a dose of 6-10 mg/kg body weight in acute and chronic disease models. Diseased mice receiving 1 at 8-10 mg/kg demonstrated a significant suppression of disease symptoms in both models. However, body weight loss was not restored in either of the models. Levels of proinflammatory cytokines (TNF-α, IFN-γ, and IL-17) were reduced significantly by 1 in mice suffering from chronic disease, while cytokine levels remained unaffected in mice with acute disease. However, the percentage of inflammatory (CD14+/CD16+) monocytes present in peripheral blood was significantly reduced (>three-fold) (p <0.05) in treatment groups relative to controls in the acute model. Histological evaluations exhibited the restoration of goblet cells, crypts, and the submucosa along with a significant reduction in monocyte aggregation in colon sections from mice receiving treatment with 1. Restoration in colon size was also observed in the treatment groups.

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