Investigation of liposome-conjugated Nuclear Factor-κB Decoy Oligodeoxynucleotide in a Mouse Model of Dextran Sodium Sulphate-induced Colitis

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  • Investigation of liposome conjugated nuclear factor kB decoy oligodeoxynucleotide in a mouse model of dextran sodium sulphate induced colitis
  • デキストラン硫酸誘発マウス大腸炎に対するリポソーム封入NF-κBデコイオリゴデオキシリボ核酸の検討
  • デキストラン リュウサン ユウハツ マウス ダイチョウエン ニ タイスル リポソーム フウニュウ NF-κB デコイ オリゴ デオキシリボ カクサン ノ ケントウ

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BACKGROUNDS/AIMS: Double strand nuclear factor-κB decoy oligodeoxynucleotide (NF-κB-Decoy) had been investigated as a potential therapeutic approach in ulcerative colitis. Here we confirm that NF-κB-Decoy inhibits inflammatory cytokines production in vitro, and report initial studies of the use of liposome-conjugated NF-κB-Decoy to treat dextran sodium sulphate (DSS)-induced colitis. METHODS: (1) Peripheral blood samples or cultured Colo 205, colon cancer cells were pretreated with NF-κB-Decoy and stimulated with lipopolysaccharide. (2) Eight-weeks-old female BALB/C mice were fed 4% DSS in drinking water for 7 days. Intra-colonic administration of liposomeconjugated NF-κB-Decoy started at the same time as DSS treatment, and continued for 14 days. RESULTS: (1) In the peripheral blood, NF-κB-Decoy significantly inhibited interleukin (IL)-6 production (Tukey test, p<0.05). In the cultured cells, NF-κB-Decoy significantly reduced IL-8 production (t-test, p<0.01). (2) During administration of DSS, mortality rate between NF-κB-Decoy treated and control mice (72.4% and 57.6% respectively) was not significantly different, and body weight loss and histopathological dameges were similar in both groups. But, after discontinuation of DSS, NF-κB-Decoytreated mice regained body weight significantly earlier than did control mice. CONCLUSIONS: NF-κB-Decoy actually inhibited IL-6 and IL-8 production in vitro. Although liposome-conjugated NF-κB-Decoy could not show amelioration in DSS mice model, NF-κB-Decoy treated mice showed earlier regain of body weight.

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