Peer-Reviewed Journal Details
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Craven, B,Zaric, V,Martin, A,Mureau, C,Egan, LJ
2015
March
Inflammatory Bowel Diseases
Effect of Genetic Deletion or Pharmacological Antagonism of Tumor Necrosis Factor Alpha on Colitis-associated Carcinogenesis in Mice
Published
WOS: 7 ()
Optional Fields
inflammatory bowel disease tumor colitis TNF- NF-B INFLAMMATORY-BOWEL-DISEASE NF-KAPPA-B EPITHELIAL-CELLS FACTOR RECEPTOR DEATH DOMAIN TNF-ALPHA PROTEIN CANCER PATHWAYS TUMORIGENESIS
21
485
495
Background:Intestinal inflammation in inflammatory bowel diseases is driven by abnormal levels of proinflammatory cytokines, where tumor necrosis factor (TNF)- seems to be particularly important. Chronic inflammatory signaling in the colon increases the risk of colorectal cancer, so we sought to evaluate the role of TNF- in a mouse model of this condition.Methods:TNF-/- mice were treated with azoxymethane/dextran sulfate sodium to induce inflammation and tumorigenesis. Etanercept was used to produce pharmacological ablation of TNF- in wild-type mice. Subsequent activation of procarcinogenic transcription factor NF-B and relevant proinflammatory cytokines of the TNF superfamily were measured through immunohistochemistry and quantitative polymerase chain reaction methods.Results:Results showed that the severity of colitis, as assessed by mortality, histological scoring, and cytokine expression levels, was similar or slightly higher in mice lacking TNF- than in control mice. Activation levels of NF-B were not influenced by the presence of TNF-. We also observed upregulated expression of TNF family member TNF-, TNF receptors 1 and 2 and a variety of other proinflammatory factors in colitis-associated tumors of TNF-/- mice, compared with levels in tumors of control mice. Neither genetic ablation of TNF- nor pharmacological inhibition of the TNF family using etanercept reduced tumor number.Conclusions:Our results reveal a redundant role for TNF- in a mouse model of colitis-associated tumorigenesis, indicating a high degree of redundancy in proinflammatory cytokine networks in this model.
10.1097/MIB.0000000000000303
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