Temporal and Spatial Analysis of Clinical and Molecular Parameters in Dextran Sodium Sulfate Induced Colitis

Abstract

BackgroundInflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn's disease (CD), are inflammatory disorders of the gastrointestinal tract caused by an interplay of genetic and environmental factors. Murine colitis model induced by Dextran Sulfate Sodium (DSS) is an animal model of IBD that is commonly used to address the pathogenesis of IBD as well as to test efficacy of therapies. In this study we systematically analyzed clinical parameters, histological changes, intestinal barrier properties and cytokine profile during the colitic and recovery phase.MethodsC57BL/6 mice were administered with 3.5% of DSS in drinking water for various times. Clinical and histological features were determined using standard criteria. Myeloperoxidase (MPO) activity, transepithelial permeability and proinflammatory mediators were determined in whole colon or proximal and distal parts of colon.ResultsAs expected after administration of DSS, mice manifest loss of body weight, shortening of colon length and bloody feces. Histological manifestations included shortening and loss of crypts, infiltration of lymphocytes and neutrophil, symptoms attenuated after DSS withdrawal. The MPO value, as inflammation indicator, also increases significantly at all periods of DSS treatment, and even after DSS withdrawal, it still held at very high levels. Trans-mucosal permeability increased during DSS treatment, but recovered to almost control level after DSS withdrawal. The production of proinflammatory mediators by colonic mucosa were enhanced during DSS treatment, and then recovered to pre-treated level after DSS withdrawal. Finally, enhanced expression of proinflammatory mediators also revealed a different profile feature in proximal and distal parts of the colon.ConclusionExperimental colitis induced by DSS is a good animal model to study the mechanisms underlying the pathogenesis and intervention against IBD, especially UC.

Effects of a Lactobacillus reuteri BR11 Mutant Deficient in the Cystine-Transport System in a Rat Model of Inflammatory Bowel Disease

“…Consumption of DSS is known to impart histological changes in the colon, including an elevated damage severity score, lengthening of crypts and crypt loss [26], often in conjunction with significant shortening of the colon [31]. Crypt lengthening and crypt loss are also commonly observed indicators of DSS-induced colitis [32], however, only crypt loss was observed in the current study.…”

Restoring Mucosal Barrier Function and Modifying Macrophage Phenotype with an Extracellular Matrix Hydrogel: Potential Therapy for Ulcerative Colitis

“…The outcomes in the DSS-colitis model can be effective in predicting clinical treatment of IBD [18]. It is well established that when DSS administration is halted, the animals will begin to spontaneously recover [50] and therefore differences among groups requires examining the temporal response. While only two markers for macrophage phenotype were used for immunolabeling, we chose the most representative marker of UC-like inflammation (TNF) and for M2-like macrophages (CD206).…”

C-Type Lectin SIGN-R1 Has a Role in Experimental Colitis and Responsiveness to Lipopolysaccharide

“…In this study, we have shown that mice deficient in the macrophage-expressed C-type lectin SIGN-R1 have IBD may arise following a loss of barrier integrity and consequential activation of the innate immune system by exposure to the indigenous intestinal flora, evoking inflammation as a result of cell infiltration ofthe colon and resulting proinflammatory cytokine release (1). In the colitis model used in this study, DSS, a sulfated polymer, induces intestinal injury by a direct toxic effect on epithelial cells of the basal crypt, with a loss of integrity in the mucosal barrier allowing infiltration of intestinal bacteria (21). Subsequently, colon inflammation develops with an infiltration of macrophages, neutrophils, and eosinophils into the colon and increased production of the inflammatory cytokines IL-1b, TNF-a, and IL-6, which contribute to the inflammation and damage to the colon (21,31).…”