Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse — A model mimicking inflammatory bowel disease

Holgersen, Kristine; Kvist, Peter Helding; Markholst, Helle; Hansen, Axel Kornerup; Holm, Thomas Lindebo

doi:10.1016/j.crohns.2013.08.002

Cited by 31 publications

(40 citation statements)

References 57 publications

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“…Intestinal inflammation was induced in WT, Il-10 −/− , Nlrp3 −/− , and Il-10 −/− Nlrp3 −/− mice by oral administration of 1.5% DSS in drinking water ad libitum for 5 days 66, 67 . Mice were separated into hypoxia and normoxia groups.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation

et al. 2017

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Hypoxia regulates autophagy and nucleotide-binding oligomerization domain receptor, pyrin domain containing (NLRP)3, two innate immune mechanisms linked by mutual regulation and associated to IBD. Here we show that hypoxia ameliorates inflammation during the development of colitis by modulating autophagy and mammalian target of rapamycin (mTOR)/NLRP3 pathway. Hypoxia significantly reduces tumor necrosis factor α, interleukin (IL)-6 and NLRP3 expression, and increases the turnover of the autophagy protein p62 in colon biopsies of Crohn’s disease patients, and in samples from dextran sulfate sodium-treated mice and Il-10 −/− mice. In vitro, NF-κB signaling and NLRP3 expression are reduced through hypoxia-induced autophagy. We also identify NLRP3 as a novel binding partner of mTOR. Dimethyloxalylglycine-mediated hydroxylase inhibition ameliorates colitis in mice, downregulates NLRP3 and promotes autophagy. We suggest that hypoxia counteracts inflammation through the downregulation of the binding of mTOR and NLRP3 and activation of autophagy.

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Section: Methodsmentioning

confidence: 99%

Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation

et al. 2017

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“…For example, guinea pigs fed degraded carrageenan develop cecal ulcerations within 21–30 days after carrageenan treatment (21), whereas germ-free guinea pigs fed carrageenan for 6 months or more do not develop any intestinal lesions (22). Concurrent treatment of conventional guinea pigs with carrageenan and metronidazole, an antimicrobial primarily active against anaerobic bacteria, has been shown to prevent the development of intestinal ulcerations (22, 23). Consistent with recent reports in human IBD (24, 25), microorganisms such as Bacteroide s vulgatus appear to play an important role in the development of the experimental ulcerative lesions in animals (26).…”

Section: The Role Of Carrageenan In Intestinal Inflammation In Animalmentioning

confidence: 99%

“…Consistent with recent reports in human IBD (24, 25), microorganisms such as Bacteroide s vulgatus appear to play an important role in the development of the experimental ulcerative lesions in animals (26). For example, animals who were immunized with B. vulgatus , prior to carrageenan administration developed experimental disease at a faster rate and more severe lesions than animals that were administered carrageenan alone (23, 27). Mirroring the development of antibodies to components of the intestinal microbiome in human IBD (28, 29), Onderdonk et al noted that non-immune carrageenan recipients developed antibodies to B. vulgatus during carrageenan treatment, implying that an adaptive immune response occurs in the animals following carrageenan-induced intestinal ulceration (26, 27).…”

Section: The Role Of Carrageenan In Intestinal Inflammation In Animalmentioning

confidence: 99%

The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation

2017

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Although the exact pathophysiology remains unknown, the development of inflammatory bowel disease (IBD) is influenced by the interplay between genetics, the immune system, and environmental factors such as diet. The commonly used food additives, carrageenan and carboxymethylcellulose (CMC), are used to develop intestinal inflammation in animal models. These food additives are excluded from current dietary approaches to induce disease remission in Crohn’s disease such as exclusive enteral nutrition (EEN) using a polymeric formula. By reviewing the existing scientific literature, this review aims to discuss the role that carrageenan and CMC may play in the development of IBD. Animal studies consistently report that carrageenan and CMC induce histopathological features that are typical of IBD while altering the microbiome, disrupting the intestinal epithelial barrier, inhibiting proteins that provide protection against microorganisms, and stimulating the elaboration of pro-inflammatory cytokines. Similar trials directly assessing the influence of carrageenan and CMC in humans are of course unethical to conduct, but recent studies of human epithelial cells and the human microbiome support the findings from animal studies. Carrageenan and CMC may trigger or magnify an inflammatory response in the human intestine but are unlikely to be identified as the sole environmental factor involved in the development of IBD or in disease recurrence after treatment. However, the widespread use of carrageenan and CMC in foods consumed by the pediatric population in a “Western” diet is on the rise alongside a corresponding increase in IBD incidence, and questions are being raised about the safety of frequent usage of these food additives. Therefore, further research is warranted to elucidate the role of carrageenan and CMC in intestinal inflammation, which may help identify novel nutritional strategies that hinder the development of the disease or prevent disease relapse post-EEN treatment.

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“…Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org). [23][24][25] Importantly, the PAC IL-10 k.o. 11,[14][15][16][17] Experimental colitis models enable dissection and individual evaluation of the various factors contributing to inflammationrelated bone loss.…”

mentioning

confidence: 99%

“…11,[14][15][16][17] Experimental colitis models enable dissection and individual evaluation of the various factors contributing to inflammationrelated bone loss. model, 24,25,29 and reference drugs with known efficacy in severe IBD are efficacious in the model. [18][19][20][21][22] Peroral administration of piroxicam induces a replicable enterocolitis in interleukin-10 knockout (IL-10 k.o.)…”

mentioning

confidence: 99%

Piroxicam Treatment Augments Bone Abnormalities in Interleukin-10 Knockout Mice

Holgersen

Dobie

Farquharson

et al. 2015

Inflammatory Bowel Diseases

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Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse — A model mimicking inflammatory bowel disease

Abstract: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research.

Cited by 31 publications

References 57 publications

Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation

Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation

The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation

Piroxicam Treatment Augments Bone Abnormalities in Interleukin-10 Knockout Mice

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