The TNBS-induced colitis animal model: An overview

Antoniou, Efstathios; Margonis, Georgios Antonios; Angelou, Anastasios; Pikouli, Anastasia; Argiri, Paraskevi; Karavokyros, Ioannis; Papalois, Αpostolos; Pikoulis, Emmanouil

doi:10.1016/j.amsu.2016.07.019

Cited by 259 publications

(222 citation statements)

References 41 publications

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“…Indeed preclinical and clinical evidence from previous studies support this possibility [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Future studies, should concentrate on which specific silymarin component(s) are most effective in other relevant pre-clinical models of IBD [10].…”

Section: Resultsmentioning

confidence: 99%

“…Of note, all of the previous experimental IBD work with silymarin (or silibinin) was conducted with a trinitrobenzene sulfonic acid [TNBS] model of colitis. This is a model of human Crohn's Disease [12][13], while the initial clinical results were obtained in patients with Ulcerative Colitis [5][6][7][8][9][10][11][12][13]. Ongoing work in our laboratory is examining the effects of silymarin derived fractions on cytokine production from colonic strips of mice with DSS colitis (a model of Ulcerative Colitis), utilizing an ex vivo system [10][11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

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Effects of Silymarin Fractions on Pro-Inflammatory Cytokine Secretion from Macrophage and Colonic Epithelial Cell Lines

Talbott¹

2017

PPIJ

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Silymarin is an extract of milk thistle seeds, consisting of four major classes of flavonoligans: silybinin, silychristin, silydianin and isosilyibinin. These compounds are known for their anti-oxidant and anti-inflammatory properties. The goal of this study was to determine if different fractions of the crude extract of silymarin inhibited proinflammatory cytokine secretion from macrophage and colonic epithelial cell lines. Methods:Milk thistle seeds were obtained from a commercial supplier. The powdered seeds (30 g) were percolated with methanol (100mL x 3). Evaporation of the solvent at reduced pressure yielded a residue. The residue was then chromatographed on a flash chromatography system. Fractions were monitored by TLC on silica gel, as described previously, and confirmed by (LC/MS) analyses. The crude silymarin extract and six distinct fractions were tested in two different cell culture systems. The secretion of TNF-α was determined from LPS-stimulated RAW 264.7 murine macrophages. We also characterized the effects of silymarin fractions on TNF-a induced chemokine (IL-8) secretion, using a HT-29 colonic epithelial cell line.Results: Fraction 5 (containing mainly silybinin and silychristin) was most potent for inhibiting TNF-α secretion from LPS-stimulated macrophages (IC50=47.7μg/ml). Fractions 2 and 4 (composed of mostly silybinin A and B) exhibited IC50 values of ≈65μg/ml in this assay. In contrast, the crude silymarin extract (IC50 value of 88.5μg/ ml) was less potent for inhibiting TNF-α secretion. The potency order of tested fractions, for inhibiting IL-8 secretion by HT-29 cells was: Fraction 2 (IC50=19.9μg/ ml) > Fraction 5 (IC50=32.8μg/ml) > Crude extract (36.1μg/ml). Summary:Silybinin and isosilybinin containing fractions of silymarin more potently inhibited pro-inflammatory cytokine secretion from macrophage and colonic epithelial cell lines. Conclusion:These data contribute to the characterization of optimal antiinflammatory flavonoligans, which can be used for follow-up testing in animal models of colitis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of Silymarin Fractions on Pro-Inflammatory Cytokine Secretion from Macrophage and Colonic Epithelial Cell Lines

Talbott¹

2017

PPIJ

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“…In this review, we will discuss the most widely used rodent models of IBD, the chemically induced colitis models, caused by dextran sulphate sodium (DSS) or trinitrobenzene sulphonic acid (TNBS), and the adoptive transfer model in mice [24,25,26,27]. …”

Section: Rodent Models Of Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Wéra

Lancellotti

Oury

2016

JCM

230

189

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Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterised by aberrant immunological responses leading to chronic inflammation without tissue regeneration. These two diseases are considered distinct entities, and there is some evidence that neutrophil behaviour, above all other aspects of immunity, clearly separate them. Neutrophils are the first immune cells recruited to the site of inflammation, and their action is crucial to limit invasion by microorganisms. Furthermore, they play an essential role in proper resolution of inflammation. When these processes are not tightly regulated, they can trigger positive feedback amplification loops that promote neutrophil activation, leading to significant tissue damage and evolution toward chronic disease. Defective chemotaxis, as observed in Crohn’s disease, can also contribute to the disease through impaired microbe elimination. In addition, through NET production, neutrophils may be involved in thrombo-embolic events frequently observed in IBD patients. While the role of neutrophils has been studied in different animal models of IBD for many years, their contribution to the pathogenesis of IBD remains poorly understood, and no molecules targeting neutrophils are used and validated for the treatment of these pathologies. Therefore, it is crucial to improve our understanding of their mode of action in these particular conditions in order to provide new therapeutic avenues for IBD.

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“…TNBS i.r. administration has been used as model for innate-driven intestinal inflammation due to epithelial damage and increased access of microbial-derived molecules to the immune cells in the lamina propria compartment (35). The use of the TNBS model that produce an acute local activation of inflammatory response allowed us to evaluate the local effect of lactate after a short term exposure, upon i.r intervention.…”

Section: Discussionmentioning

confidence: 99%

Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model

et al. 2016

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Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far, in vivo effects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that flagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties.

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The TNBS-induced colitis animal model: An overview

Cited by 259 publications

References 41 publications

Effects of Silymarin Fractions on Pro-Inflammatory Cytokine Secretion from Macrophage and Colonic Epithelial Cell Lines

Effects of Silymarin Fractions on Pro-Inflammatory Cytokine Secretion from Macrophage and Colonic Epithelial Cell Lines

The Dual Role of Neutrophils in Inflammatory Bowel Diseases

Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model

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