title: Opposite role of tumor necrosis factor receptors in dextran sulfate sodium-induced colitis in mice.
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.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Central South University, Changsha, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.forename: Yan
authors.initials: Y
authors.lastname: Dou
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Guijun
authors.initials: G
authors.lastname: Liu
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Shi
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000502:physiology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D015431:Weight Loss / Q000235:genetics
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate