DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat

Abstract

Inflammatory Bowel Diseases (IBD), including Crohn's Disease and Ulcerative Colitis, have long been associated with a genetic basis, and more recently host immune responses to microbial and environmental agents. Dinitrobenzene sulfonic acid (DNBS)-induced colitis allows one to study the pathogenesis of IBD associated environmental triggers such as stress and diet, the effects of potential therapies, and the mechanisms underlying intestinal inflammation and mucosal injury. In this paper, we investigated the effects of dietary n-3 and n-6 fatty acids on the colonic mucosal inflammatory response to DNBS-induced colitis in rats. All rats were fed identical diets with the exception of different types of fatty acids [safflower oil (SO), canola oil (CO), or fish oil (FO)] for three weeks prior to exposure to intrarectal DNBS. Control rats given intrarectal ethanol continued gaining weight over the 5 day study, whereas, DNBS-treated rats fed lipid diets all lost weight with FO and CO fed rats demonstrating significant weight loss by 48 hr and rats fed SO by 72 hr. Weight gain resumed after 72 hr post DNBS, and by 5 days post DNBS, the FO group had a higher body weight than SO or CO groups. Colonic sections collected 5 days post DNBS-treatment showed focal ulceration, crypt destruction, goblet cell depletion, and mucosal infiltration of both acute and chronic inflammatory cells that differed in severity among diet groups. The SO fed group showed the most severe damage followed by the CO, and FO fed groups that showed the mildest degree of tissue injury. Similarly, colonic myeloperoxidase (MPO) activity, a marker of neutrophil activity was significantly higher in SO followed by CO fed rats, with FO fed rats having significantly lower MPO activity. These results demonstrate the use of DNBS-induced colitis, as outlined in this protocol, to determine the impact of diet in the pathogenesis of IBD. Video LinkThe video component of this article can be found at

The Immunomodulatory Properties of Propyl‐Propane Thiosulfonate Contribute to its Intestinal Anti‐Inflammatory Effect in Experimental Colitis

“…DNBS colitis is also characterized by an intense impairment of the epithelial barrier integrity . Accordingly, the markers used to evaluate this intestinal function, including the mucin Muc2 , occludin ( Ocln ) and the trefoil factor ( Tff )‐ 3 , were profoundly modified in DNBS‐colitic mice compared to noncolitic mice.…”

Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice

“…SNU-171123-2), and the protocols were performed in accordance with approved guidelines. Two different mouse models for IBD were used for this study (dextran sulfate sodium (DSS)-, and dinitrobenzene sulfonic acid (DNBS)-induced colitis models), and each colitis model was made as previously described (Kim et al, 2013;Martín et al, 2014;Morampudi et al, 2014;Solomon et al, 2010). For the first experiment, colitis was induced by 3% DSS (36-50 kDa; MP Biomedical, Solon, OH, USA) in the drinking water from day 0 to day 7, whereas mice offered normal water were used as the naive group.…”

Fatty acids as modulators of neutrophil recruitment, function and survival

“…Neutrophils cultured with increasing concentrations of linoleic acid (6.25 to 100 ȝg/ml) during 2 h showed reduced ATP production, increased lactate dehydrogenase release, indicating a cytotoxic activity (Lux et al, 2009) Linoleic acid leads to recruitment of neutrophils to inflammed areas (Hekmatdoost et al, 2013;Morampudi et al, 2014;Rodrigues et al, 2012) even in sterile conditions (Rodrigues et al, 2010). This effect was acompained by an elevation in the expression of neutrophil adhesion molecules (L-selectin) and increase in endothelium-neutrophil interactions (Mena et al, 2013;Rodrigues et al, 2010).…”