Amelioration of murine dextran sulfate sodium-induced colitis by nuclear factor-κb decoy oligonucleotides

• Published in: The American journal of surgery 2009-06, Vol.197 (6), p.797-805
• Main Authors: Xiang, Jun Ying, M.D, Wu, Li Guo, M.D, Huang, Xiao Li, M.D, Zhang, Meng, M.D, Pen, Lan, M.D, Ouyan, Qin, M.D, Gan, Hua Tian, M.D., Ph.D
• Format: Article
• Language: English
• Subjects: Binding; Binding sites; Biological and medical sciences; Colon; Cytokines; Deoxyribonucleic acid; Dextran; Dextran sulfate; Dextran sulfate sodium-induced colitis; DNA; Electrophoretic mobility; Enzyme-linked immunosorbent assay; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; General aspects; IL-1β; Inflammation; Inflammatory bowel disease; Interleukins; Medical sciences; Mice; Nuclear factor-κB decoy ODNs; Oligonucleotides; Other diseases. Semiology; Pathogenesis; Peroxidase; Polymerase chain reaction; Reverse transcription; Sodium; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; Sulfates; Surgery; TNF inhibitors; Transcription factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ulcerative colitis
• ISSN: 0002-9610; 1879-1883
• DOI: 10.1016/j.amjsurg.2008.04.012

Abstract Background Activation of nuclear factor (NF)-κB has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). The purpose of the current study was to investigate the effects of NF-κB decoy oligonucleotides (ODNs) on an experimental model of UC. Methods NF-κB decoy ODNs were administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay (EMSA). The expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results A significant improvement was observed in DAI and histological score in mice with NF-κB decoy ODNs, and the increase in NF-κB DNA binding activity, myeloperoxidase (MPO) activity, IL-1β, and TNF-a in mice with DSS-induced colitis was significantly reduced following administration of NF-κB decoy ODNs. Conclusions The administration of NF-κB decoy ODNs leads to an amelioration of DSS-induced colitis, suggesting administration of NF-κB decoy ODNs may provide a therapeutic approach for UC.