Pwe109 a metabolomic profiling study of a chemically. White paper selecting an appropriate chemicallyinduced. Then i will give an overview of the different experimental colitis models that are currently used. The aim of the present study was to test the intestinal antiinflammatory activity of apigenin k, a soluble form of apigenin, in two models of rat colitis, namely the trinitrobenzenesulfonic acid tnbs model and the dextran sulphate sodium dss model. A guide to histomorphological evaluation of intestinal. Chemically induced mouse models of colitis request pdf. Other applications for chemically induced colitis model table 1. These include trinitrobenzene sulfonic acid tnbs, oxazolone, and acute or chronic dextran sodium sulfate dss colitis models. Using mouse models of citrobacter rodentium, which closely mimics human diarrheal pathogens inducing host intestinal inflammation, and campylobacter jejuni infection, as well as chemically and genetically induced models of intestinal inflammation, we demonstrate that hostmediated inflammation in response to an infecting agent, a chemical. Induction of inflammatory bowel disease in immunodeficient mice by depletion of regulatory t cells. Uncovering pathogenic mechanisms of inflammatory bowel disease. Ecibat model of chronic intestinal inflammation was chosen because it induces a colonic inflammation which is closer to human ibd than other chemicallyinduced colitis models. Evaluating 11cpbr28 pet for monitoring gut and brain.
Cyclooxygenase2 cox2 inhibition prevents adenoma formation in humans and mouse models of colon cancer. Murine models of inflammatory bowel disease ibd sage journals. Wirtz s, popp v, kindermann m, gerlach k, weigmann b, fichtnerfeigl s, neurath mf. The most common experimental colitis is induced by dss. Mouse models of colorectal cancer and intestinal cancer are experimental systems in which mice are genetically manipulated, fed a modified diet, or challenged with chemicals to develop malignancies in the gastrointestinal tract. Intestinal barrier dysfunction orchestrates the onset of. Currently, chemically induced colitis models belong to one of the most commonly used mouse ibd models since the onset of inflammation is immediate and the procedure is generally straightforward. Mouse models of intestinal inflammation can be widely grouped into chemically induced models.
Methods c57bl6 female mice at 910 weeks old were administered 4. Furthermore, fxr activation inhibits proinflammatory cytokine production in vivo in the mouse colonic mucosa, and ex vivo in different immune cell populations. Highresolution magnetic resonance colonography and dynamic contrastenhanced magnetic resonance imaging in a murine model of colitis. This targeted approach, which in itself is biased, means that murine genetic diversity and sexrelated differences are ignored, making it even more difficult to extend findings. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen. Comparison of experimental mouse models of inflammatory bowel. Chemically induced mouse models of acute and chronic.
We determined to use 2% wtvol of dss 40 kda in this study, based on the most. Frontiers an orally active cannabis extract with high. Chemical induced mouse models of intestinal inflammation. Because apn appears to be a critical factor in regulating cell proliferation as well as inflammation in atherosclerosis, 7 x 7 shimada, k. In this process, intestinal epithelial cells play important roles linking innate and acquired immune responses. The chemically induced models to study ibd are the models studied in greatest.
Chemicalinduced models of gut inflammation are the most commonly used and best described models of ibd. Conclusions fxr activation prevents chemically induced intestinal inflammation, with improvement of colitis symptoms, inhibition of epithelial permeability, and reduced goblet cell loss. Biomedicines free fulltext physalis angulata calyces. Colitis induced with 2,4,6trinitrobenzenesulfonic acid tnbs is a widely used model to monitor temporal changes in inflammatory markers and other symptoms characteristic for uc. Intestinal antiinflammatory activity of apigenin k in two. Anecdotal and scientific evidence suggests that cannabis use may be beneficial in inflammatory bowel disease ibd patients. Chemical and pathogeninduced inflammation disrupt the. We profiled gut microbial diversity by sequencing 16s ribosomal ribonucleic acid rrna genes from fecal and cecal samples.
Tnbsethanol enemainduced colitis is associated with chemically. Franco biological evaluation of promising substances group, department of pharmaceutical sciences, university of cartagena, carrera 50 no. Mechanisms of intestinal inflammation and development of. Extracts from boswellia serrata have been reported to have antiinflammatory activity, primarily via boswellic acidmediated inhibition of leukotriene synthesis. Spontaneous models represent one of the most attractive model systems for studying intestinal in. Intracolonic tnbs administration causes chemically induced damage of the intestinal mucosa.
Clinical parameters of body weight loss, stool consistency and presence of rectal bleeding were assessed daily. Pdf investigating intestinal inflammation in dssinduced. Here, we provide detailed protocols of these two mouse models of experimentally induced intestinal inflammation. Mouse models of intestinal inflammation as tools to. Lactobacillus paracasei reduces intestinal inflammation in. Murine colitis models are crucial tools for understanding intestinal homeostasis and inflammation. Wirtz s1, popp v1, kindermann m1, gerlach k1, weigmann b1, fichtnerfeigl s2, neurath mf1. A versatile new model of chemically induced chronic.
We have learned a great deal from these models about the. Chemical models and ibd 281 chemical induced models of chronic intestinal inflammation 2, 4, 6trinitrobenzene sulfonic acid tnbs tnbs elicits cellmediated immune responses and induces transmural inflammation in the gut with morphological and histopathological features similar to those of human ibd 18,35. Experimental colitis can be induced using chemical irritant or bacterial infection. Investigating intestinal inflammation in dssinduced model of ibd. Chemically induced mouse models of colitis waldner. Sharif shajib and marcus m manocha and waliul i khan, journaljournal of visualized experiments. Veterinary pathology image analysisbased approaches the. Mistakes in mouse models of ibd and how to avoid them. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Flavonoids are polyphenolic compounds that are widespread in nature, and consumed as part of the human diet in significant amounts. Gasdermin e gsdme, also known as deafness autosomal dominant 5 dfna5 and previously identified to be an inducer of regulated cell death, is frequently epigenetically inactivated in different cancer types, suggesting that gsdme is a tumor suppressor gene. Insights from advances in research of chemically induced. During this talk i will introduce you to the inflammatory bowel diseases. In this report, we investigated the role of apn in regulating intestinal inflammation using chemically induced models of inflammatory colitis in mice.
Assessing mucosal inflammation in a dssinduced colitis. Inflammatory bowel diseases ibds result in diarrhea and abdominal pain with further potential complications such as tissue fibrosis and stenosis. Our understanding of ibd depends largely on rodent models. This screen is designed to detect mutants with increased susceptibility to colitis induced by the chemical dextran sulfate sodium dss. Mouse models of ibd are effective and highly used models based on their pathology, immune response, wellunderstood genetic backgrounds, and relatively low cost. Chemically induced animal models of colitis can be quite useful, however, for the study of acute colonic tissue injury and repair mechanisms, or when paired. Download figure download powerpoint ninetyeight vocs were identified in the headspace of the colonic content collected during necropsy at d 0 n 11, 5 n 11, 8 n 11, and 11 n 7 of acute dssinduced colitis. Acute colitis was induced by rectal application of tnbs or oxazolone to sensitized mice and oral. Adiponectin deficiency protects mice from chemically. However, most current models utilize a highly inbred strain of mice, and often only one sex is employed to limit bias. Request pdf chemical induced mouse models of intestinal inflammation animal models of intestinal inflammation are indispensable for our understanding of. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Potential role of fecal volatile organic compounds as. Rodent chemicallyinduced models of ibd, primarily mouse but also rat, are commonly used in drug discovery programs.
A cbaj mouse model was used to evaluate intestinal responses to salmonellainduced inflammation. Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent inflammatory bowel diseases, vol. Several new mouse ibd model systems derived from gene. Physalis angulata calyces modulate macrophage polarization and alleviate chemically induced intestinal inflammation in mice by david rivera, yanet ocampo and luis a.
Mouse models of acute and chronic colitis springerlink. Over the years, many transgenic tg and gene knockout ko mouse strains have been developed. In parallel, we evaluated chemically induced inflammation by dextran sodium sulfate dss and a noninflammation control. Chemically induced mouse models of acute and chronic intestinal. Chemically induced mouse models of acute and chronic intestinal inflammation. Here, we have investigated the effect of a standardized cannabis sativa extract with high content of cannabidiol cbd, here named cbd bds for cbd botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Effects of boswellia serrata in mouse models of chemically. Animal models of colitis range from those arising spontaneously in susceptible strains of certain species to those requiring administration of specific concentrations of colitisinducing chemicals, such as dextran sulphate sodium dss. Ibd can be induced in mice by dextran sulfate sodium dss or by a 2,4. An experimental model of colitis induced by dextran. These models enable researchers to study the onset, progression of the disease, and understand in depth the molecular events that contribute to the development and. Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent. Chemically induced mouse models of intestinal inflammation.
Farnesoid x receptor activation inhibits inflammation and. Mice were culled at days 0 n 11, 5 n 11, 8 n 11 and 11 n 8. To recreate the dssinduced intestinal inflammation that has been demonstrated in mouse models 25, 26, we introduced dss to the luminal compartment of the villi, mimicking the gavage of dss in a mouse model. Protective effects of dietary curcumin in mouse model of. St11 feeding was not associated with significant difference in body weight before colitis induction as compared to vehicle pbsfed mice figure 3a lower part. Using chemically induced chronic colon inflammation in an outbred strain of mice rjorl. Chemically induced mouse models of acute and chronic intestinal inflammation article in nature protocols 127. Investigating intestinal inflammation in dssinduced model. Chemicallyinduced intestinal inflammation in mice has been used to model aspects of human inflammatory bowel disease ibd, and has provided insights into the mechanisms of disease. The pathophysiology of the model is the result of an interaction involving both intrinsic factors characteristics of the animal physiology such as genetic and immunological background and extrinsic factors manipulations and methodologies inducing intestinal inflammation. Here we present an updated version of a protocol we published in 2007 for key models of acute and chronic forms of colitis induced by 2,4,6trinitrobenzene sulfonic acid tnbs, oxazolone and. All models of chemically induced colonic inflammation start from a disrupted epithelial barrier enabling an immunoreactive agent to interact with immune cells within the lamina propria. Several chemically induced animal models are used to mimic uc in humans.
Insights from mouse models of colitis leukocyte biology. Dextran sodium sulphate dss dextran sulphate sodium dssinduced colitis is a reproducible model that morphologically and symptomatically resembles ulcerative colitis in humans 49,50. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli. Chemically induced mouse models of ibd are one of the most commonly used models because they are easy to induce, the onset, duration, and severity of inflammation are immediate and controllable 14,15. Mouse model of colorectal and intestinal cancer wikipedia. In this study, we aimed to evaluate the tumorsuppressive effects of gsdme in two intestinal cancer mouse models. Mustafi d, fan x, dougherty u, bissonnette m, karczmar gs, oto a, hart j, markiewicz e, zamora m. In three small clinical trials, boswellia was shown to improve symptoms of ulcerative colitis and crohns disease, and because of its alleged safety, boswellia was considered superior over mesalazine in terms of a benefitrisk evaluation. Chemically induced ibds and associated colorectal cancer development via aom or dmh injections followed by dss and dnbstnbsethanol administration have been. Mice with liverspecific overexpression of solublecd86igfcfusionproteindevelopedtransmural colitisby810weeksofage33. Dssinduced intestinal inflammation in mice and t cell transfer colitis in scid mice are most widely used and accepted models that can recapitulate the human diseases.
As the onset of inflammation is immediate and the procedure is relatively straightforward, chemically induced models of intestinal inflammation belong to. Additionally, dss model of colitis is one of the widely used models as it can be easily developed owing to the wide availability and low cost of dss. Animal models of ulcerative colitis and their application. Here, we provide protocols for establishing murine 2,4,6trinitro benzene sulfonic acid tnbs, oxazolone and both acute and chronic dextran sodium sulfate dss colitis, the most widely used chemically induced models of intestinal inflammation. Animal models of inflammatory bowel disease hstalks. Animal models to study acute and chronic intestinal inflammation in. Detailed in this unit is a description of the most commonly used chemically induced mouse models of ibd.466 1494 643 894 667 1469 82 46 442 701 979 1242 1334 1100 1326 1443 978 1333 851 1278 1117 318 1031 1247 1027 986 301 876 1604 591 996 394 527 570 633 296 1329 632 325 1250 895 396 170 534 989 535 900 749