Therapeutic effect of intracolonically administered nuclear factorκB (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis

Abstract

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.

Interleukin 6 inhibition by triptolide prevents inflammation in a mouse model of ulcerative colitis

“…According to the standard by Murano et al (29), the DAI score was calculated as follows: DAI=(score of body weight loss + score of stool properties + score of hematochezia)/3.…”

Peroxisome proliferator-activated receptor-γ is downregulated in ulcerative colitis and is involved in experimental colitis-associated neoplasia

“…At the end of first week, the clinical disease activity index (DAI) was measured using the previously described protocol (14). The DAI ranged between 0 and 4 and was calculated from the sum of scores provided for percentage loss of body weight, stool consistency and presence or absence of fecal blood.…”

Effect of secondary lymphoid tissue chemokine suppression on experimental ulcerative colitis in mice

“…The disease activity index (DAI) was determined by scoring the extent of body weight loss, stool consistency, and gross bleeding, according to the method described by Murano et al (2000). The formula to calculate DAI was as follows: (combined score of weight loss, stool consistency, and bleeding)/3.…”