Opposite role of tumor necrosis factor receptors in dextran sulfate sodium-induced colitis in mice

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

doi:10.1371/journal.pone.0052924

Opposite role of tumor necrosis factor receptors in dextran sulfate sodium-induced colitis in mice

PLoS One. 2012;7(12):e52924. doi: 10.1371/journal.pone.0052924. Epub 2012 Dec 28.

Authors

Ke Wang¹, 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

Affiliation

¹ Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, P. R. China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / genetics
Cells, Cultured
Dextran Sulfate / pharmacology
Inflammatory Bowel Diseases / chemically induced
Inflammatory Bowel Diseases / genetics
Inflammatory Bowel Diseases / metabolism*
Intestinal Mucosa / drug effects
Intestinal Mucosa / metabolism
Intestinal Mucosa / physiology
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Tumor Necrosis Factor, Type I / genetics
Receptors, Tumor Necrosis Factor, Type I / physiology*
Receptors, Tumor Necrosis Factor, Type II / genetics
Receptors, Tumor Necrosis Factor, Type II / metabolism
Receptors, Tumor Necrosis Factor, Type II / physiology*
Survival Analysis
Tumor Necrosis Factor-alpha / pharmacology
Tumor Necrosis Factor-alpha / physiology
Weight Loss / genetics

Substances

Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha
Dextran Sulfate

Grants and funding

This work was supported by grants from the National Key Basic Research Program of China (2007CB512406; 2009CB522408) and the National Natural Science Foundation of China (30801029, 81072475 and 81172800). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.