Temporal proteomic analysis of acute Dextran Sulfate Sodium-induced colitis

Authors

• N Schneider
• SR Burks
• AH Paz
• JA Frank

Abstract

Dextran Sulfate Sodium (DSS)-induced colitis is a chemical model largely used for its reproducibility and resemblance to human Ulcerative Colitis (UC). The chemical triggers exacerbated immune response due to damage to the colonic epithelial layer with the involvement of Th1, Th2 and Th17 responses. Nevertheless, a more detailed proteomic profile of the disease is still necessary to facilitate development of novel therapies. Acute colitis was induced by administration of DSS 1, 2 or 3% in drinking water for 7 days. C56Bl/6 mice were monitored daily, while spleens and colon samples were collected at the end of the experiment. DSS 3% produced the most consistent model of UC clinically and histologically with colon shortening and spleen weight. Following a time course analysis, colon length started to diminish at day 3, and spleen weights were significantly increased at days 6 and 8. A panel of cytokines/chemokines was analyzed in colon samples. Inflammatory factors started to increase starting at days 4 and 5, that correlated to the worsening of clinical symptoms. Classical Th1/Th17 cytokines (TNF, IL-6, IL-17, KC, IL-1), Th2 cytokines (IL-9, IL-5) and other inflammatory factors (RANTES, MCP-1, LIF, Eotaxin, MIP2, G-CSF, MIP-1, MIP-1, MIG, LIX, IFN, IL-1) were progressively upregulated, characterizing an exacerbated immune response. Our findings show that the severity of experimental colitis is dependent on DSS concentration, and that the buildup of inflammatory factors is correlated to worsening of clinical symptoms. Further analysis of histology and immune cellular profile will be carried out.

Scientific Focus Area: Immunology

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