Opposite Role of Tumor Necrosis Factor Receptors in Dextran Sulfate Sodium-Induced Colitis in Mice

• DOI: 10.1371/journal.pone.0052924
• Publication Date: 2012-12-28T22:23:35Z
• Authors: Ke Wang; Gencheng Han; Yan Dou; Yi Wang; Guijun Liu; Renxi Wang; He Xiao; Xinying Li; Chunmei Hou; Beifen Shen; Renfeng Guo; Yan Li; Yanchun Shi; Guojiang Chen
• Keywords: Mice, Knockout; 0301 basic medicine; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha; Science; Q; Dextran Sulfate; R; Apoptosis; Inflammatory Bowel Diseases; Survival Analysis; 3. Good health; Mice; 03 medical and health sciences; Receptors, Tumor Necrosis Factor, Type I; Weight Loss; Medicine; Animals; Receptors, Tumor Necrosis Factor, Type II; Intestinal Mucosa; Cells, Cultured; Research Article

Tumor necrosis factor-α (TNF-α) is a key factor for the pathogenesis of inflammatory bowel diseases (IBD), whose function is known to be mediated by TNF receptor 1 (TNFR1) or 2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, acute colitis was induced by dextran sulfate sodium (DSS) instillation in TNFR1 or 2-/- mice. TNFR1 ablation led to exacerbation of signs of colitis, including more weight loss, increased mortality, colon shortening and oedema, severe intestinal damage, and higher levels of myeloperoxidase compared to wild-type counterparts. While, TNFR2 deficiency had opposite effects. This discrepancy was reflected by alteration of proinflammatory cytokine and chemokine production in the colons. Importantly, TNFR1 ablation rendered enhanced apoptosis of colonic epithelial cells and TNFR2 deficiency conferred pro-apoptotic effects of lamina propria (LP)-immune cells, as shown by the decreased ratio of Bcl-2/Bax and enhanced nuclear factor (NF)-κB activity.