SUMMARYCytokines such as IL-1, tumour necrosis factor-alpha (TNF-a ), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor kB (NF-kB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NFkB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-a concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-kB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-kB antisense oligonucleotide may be effective in ulcerative colitis.

The pan-colonic NBI system improves the total number of adenomas detected, including significantly more diminutive adenomas, without prolongation of extubation time. These results indicate that routine use of the NBI system for surveillance of diminutive adenomas may be recommended.

Expression of the EP4 receptor, a prostaglandin (PG)E2 receptor subtype, as well as disease suppression by the administration of a selective EP4 agonist (ONO-AE1-329) was investigated in the colorectal mucosa of rats with dextran sodium sulphate (DSS)-induced colitis. Rats were given drinking water containing 3% DSS for 2 weeks. Expression of EP4 receptor mRNA was barely detectable under normal conditions according to reverse transcription-polymerase chain reaction (RT-PCR). By 1 week after the initial administration of DSS, the receptor mRNA was strongly expressed. After ONO-AE1-329 was administered intracolonically to rats with DSS colitis for 7 consecutive days, erosion and ulceration decreased. Peripheral white blood cell (WBC) counts became less elevated. Interleukin (IL)-1b and growth-regulated gene product/cytokine-induced neutrophil chemoattractant (GRO/CINC-1) concentrations in colorectal mucosa were lower than in colitis control group (IL-1b: 12.8 AE 4.6 and 30.8 AE 6.2 mg/mg protein, P < 0.05; GRO/CINC-1: 15.5 AE 3.0 and 39.2 AE 5.4 mg/mg protein, P < 0.05), and the expression of the corresponding cytokine mRNA was strongly suppressed. IL-10 concentration was higher than in control group (14.5 AE 1.7 and 7.9 AE 1.2 mg/mg, P < 0.05), and the mRNA was more strongly expressed. These results suggest that the EP4 receptor is important in colonic inflammation, and that PGE2 suppresses DSS colitis at least partly via the EP4 receptor and the above cytokine changes. Intracolonic administration of selective EP4 agonist might have therapeutic applicability in inflammatory bowel disease such as ulcerative colitis.

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