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.
Highlights
Tumor necrosis factor (TNF) plays a crucial role in immune response at physiological and pathological states, which is based on its pleiotropic function on differentiation, growth and apoptosis of both immune and non-immune cell populations [1,2]
At day 8, 57% (16/28) of TNF-R12/2, 86% (31/36) of TNF-R22/2 mice had survived, whereas survival was 80% (16/ 20) in wild type (WT) mice (Fig. 1B). These results indicate that TNF-R12/2 mice exhibit more weight loss and mortality, while TNF-R2 deficiency attenuates the symptoms of colitis
TNF plays a critical role in the immunopathogenesis of inflammatory bowel diseases (IBD)
Summary
Tumor necrosis factor (TNF) plays a crucial role in immune response at physiological and pathological states, which is based on its pleiotropic function on differentiation, growth and apoptosis of both immune and non-immune cell populations [1,2]. The polymorphisms in the TNF-R2 gene have been reported to be associated with a higher susceptibility to Crohn’s disease (CD) [8] These observations strongly support a disease-promoting role of TNF signaling via TNF-R2 during IBD development. Our recent study has shown that TNF signaling via TNFR1or TNF-R2 play a pathogenic role in TNBS-induced colitis [12]. Overall, these studies underline the complexity of TNF bioactivity via TNF-R1 or 2 during the onset and perpetuation of intestinal inflammation, which may be affected by different TNFR expression patterns and distinct colitis models used
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
