The Effects Of NF-κB Decoy Oligonucleotides On Dextran Sulphate Sodium (DSS)-induced Colitis

Background and AimsThe exact pathogenesis of ulcerative colitis (UC) remain unclear. Activation of nuclear factor(NF)-κB, which controls transcription of various proinflammatory cytokine genes, has been shown to play a key role in the pathogenesis of UC. The purpose of present study was to investigate the effects of NF-κB decoy oligonucleotides(ODN) on dextran sulphate sodium (DSS)-induced colitis in mice. MethodsA total of 36 female BABL/C mice was randomly divided into four groups. One of the four groups was only fed with distilled water and the other three groups were fed with 5% DSS solution, which had been demonstrated to be able to induce colitis in mice. One group of DSS-induced colitis was administrated with 0.15ml saline. Saline was replaced with 0.15ml NF-κB decoy ODN (25nmol) or 0.15ml NF-kB scrambled decoy ODN(25nmol)in the other 2 groups of DSS induced colitis. Colitis was evaluated by disease active index(DAI) and histological score. TNF-α levels were measured by enzyme linked immunosorbent assay(ELISA).NF-KB expression was determined by immunohistochemical staining. The distribution of NF-κB decoy ODN was investigated by confocal laser microscopy.Rusults1. DAI and histological score were markedly increased after the administration of 5%DSS compared with normal control(P<0.05),and the treatment of NF-kB decoy ODN reduced significantly the DAI and histological score.2. TNF-a levels were markedly increased after the administration of 5%DSS compared with normal control(P<0.05),and the treatment of NF-kB decoy ODN reduced significantly TNF-a levels.3. In sections from mice who were treated with 5%DSS plus NF-kB decoy ODN or NF-kB scramble decoy ODN, most of the NF-KBp65 positive cells displayed nuclear staining and only a few cells showed positive cytoplasm staining. There were no significant differences in NF-kB expression among these 3 groups, hi contrast,in sections from mice who were not treated with 5%DSS,NF-kB was mainly found in the cytoplasm and little staining was detected in the nucleus.4. The confocal laser microscopy showed that NF-kB decoy ODN could be ingested efficiently into the mucosa and submucosa of colon. ConclusionsOur results suggest that NF-kB pathway is associated with pathogenesis of DSS-induced colitis which is very similar to human UC. The blockade of NF-kB pathway by NF-kB decoy ODN improved DAI and histological score, and reduced TNF-a levels in DSS-induced colitis in mice, indicating that NF-kB decoy ODN could be useful for the treatment of UC.