Unique dietary-related mouse model of colitis

Bernstein, Harris; Holubec, Hana; Bernstein, Carol; Ignatenko, Natalia A.; Gerner, Eugene W.; Dvorak, Katerina; Besselsen, David G.; Ramsey, Lois; Dall'Agnol, Monique; Blohm-Mangone, Karen; Padilla-Torres, Jose L.; Cui, Haiyan; Garewal, Harinder S.; Payne, Claire M.

doi:10.1097/01.mib.0000209789.14114.63

Cited by 42 publications

(45 citation statements)

References 83 publications

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“…Previously, we reported that mice fed a diet supplemented with 0.2% DOC developed colonic inflammation associated with increased nitrosative stress, as well as increased angiogenesis, oxidative DNA/RNA damage, and proliferation [6]. Consistent with these findings, there was an increase in expression of numerous genes which likely play a role in inflammation.…”

Section: Introductionsupporting

confidence: 60%

Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles

et al. 2007

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Nos2 knockout mice were compared to wild-type mice for susceptibility to colitis in response to a diet supplemented with deoxycholate, a bile acid increased in the colon of individuals on a high-fat diet. Wild-type mice fed a fat-related diet, supplemented with 0.2% DOC, develop colonic inflammation associated with increases in nitrosative stress, proliferation, oxidative DNA/RNA damage, and angiogenesis, as well as altered expression of numerous genes. However, Nos2 knockout mice fed a diet supplemented with deoxycholate were resistant to these alterations. In particular, 35 genes were identified whose expression was significantly altered at the mRNA level in deoxycholate-fed Nos2(+/+) mice but not in deoxycholate-fed Nos2(-/-) mice. Some of these alterations in NOS2-dependent gene expression correspond to those reported in human inflammatory bowel disease. Overall, our results indicate that NOS2 expression is necessary for the development of deoxycholate-induced colitis in mice, a unique dietary-related model of colitis.

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Section: Introductionsupporting

confidence: 60%

Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles

et al. 2007

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“…Adenomatous injury was also reported by Payne et al 14 besides alterations of chronic colitis type, with no statistically significant differences between groups, in a study conducted for a period of eight months. These results were also found by Bernstein et al 15 .…”

Section: Macroscopic Pathological Changessupporting

confidence: 81%

Secondary bile acids effects in colon pathology. Experimental mice study

Molnar

Russu

et al. 2015

Acta Cir. Bras.

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PURPOSE:To assess whether deoxycholic acid (DOC) and lithocholic acid (LCA) administered in a period of six months in a concentration of 0.25% may have a carcinogenic role in mice colon. METHODS:The study used C57BL6 female mice divided into four groups. The control group received a balanced diet and the others received diets supplemented with 0.25% DOC, 0.25% LCA and 0.125% DOC+0.125% LCA, respectively. After euthanasia, the lesions found in the resected gastrointestinal tracts were stained with hematoxylin-eosin and examined microscopically. RESULTS:No gastrointestinal tract changes were observed in the control group, while hyperplastic Peyer's patches in the small intestine, flat adenomas with mild dysplasia and chronic colitis at the level of the colon were found in all three test groups. The colonic lesions prevailed in the proximal colon. The highest number of flat adenoma lesions (8), hyperplasia of Peyer's patches (25) and chronic colitis (2) were found in mice fed with diet and LCA. CONCLUSION:Precancerous or cancerous pathological lesions could not be identified. Instead, adenomatous colonic injuries occurred in a shorter period of time (six months), compared to the reported data.

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“…This suggests that, in a model of disease where impaired acute inflammation exists, bile acids alone may be sufficient to result in intestinal mucosal damage that triggers inflammatory bowel disease. In another model, supplementation with the secondary bile acid deoxycholate alone was sufficient to induce colitis, even in wild-type mice [105].The hygiene hypothesis suggests that early exposure to a wide variety of intestinal pathogens is protective against the development of CD in later life, while increasingly sanitized environments increase the risk of CD development [106]. These observations may …”

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confidence: 81%

Section: Lifestyle Factors May Influence Intestinal Barrier and Innate mentioning

confidence: 99%

Crohn’s disease as an immunodeficiency

Hayee

Rahman

Sewell

et al. 2010

Expert Review of Clinical Immunology

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The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools. Keywordsbacteria; Crohn's disease; immunodeficiency; innate immunity; macrophage; neutrophil Established intestinal lesions in Crohn's disease (CD) contain a massive, mixed inflammatory cell infiltrate associated with a complex storm of cytokines in a selfperpetuating, chronic inflammatory response [1][2][3]. Most research to date has focused on the the immunological characteristics of established lesions and drawn inferences about their initiation. The predominance of a classically Th1-associated cytokine profile in these lesions led to the assumption that T lymphocytes were central to the initial pathogenesis. More recently, the role of regulatory (Treg) FoxP3 + and IL-23-induced responsive Th17-type T lymphocytes has gained popularity [2,4,5]. Treg cell populations are diminished in patients with CD [6] and, although the hypothesis of CD as an immunodeficiency does not necessarily exclude defects in T-cell function, to date, no convincing intrinsic (primary) defect has been identified to implicate these cells in the pathogenesis of human CD.The hypothesis that immunodeficiency underpins the development of CD seems, at first, to be in direct contrast with histological observations of established intestinal lesions and the † Author for correspondence: Tel.: +44 207 679 6170 Fax: +44 207 679 0967 b.hayee@nhs.net. Financial & competing interests disclosure The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Europe PMC Funders Group Association between immunodeficiency diseases & CDThere is a well-known and strong association between primary immunodeficiency disorders and non-infectious granulomatous intestinal inflammation. Chronic granulomatous disease (CGD), glycogen storage disease type 1b, leukocyte adhesion deficiency, Chediak-Higashi and Hermansky-Pudlak syndromes are all strongly associated with intestinal inflammation that is indistinguishable from CD [...

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Unique dietary-related mouse model of colitis

Cited by 42 publications

References 83 publications

Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles

Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles

Secondary bile acids effects in colon pathology. Experimental mice study

Crohn’s disease as an immunodeficiency

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