Nuclear factor-kappa B activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin

Herfarth, Hans and Brand, K. and Rath, H. C. and Rogler, Gerhard and Schoelmerich, Juergen and Falk, Werner (2000) Nuclear factor-kappa B activity and intestinal inflammation in dextran sulphate sodium (DSS)-induced colitis in mice is suppressed by gliotoxin. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 120 (1). pp. 59-65. ISSN 0009-9104

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Abstract

In acute DSS-induced colitis nuclear factor (NF)-kappa B-dependent inflammatory cytokines including IL-1 and tumour necrosis factor-alpha (TNF-alpha) are up-regulated. Here we examined the effects of gliotoxin, a fungal metabolite known to inhibit NF-kappa B activity, on cytokine production by a mouse cell system in vitro and on intestinal inflammation and NF-kappa B activation in vivo. In vitro gliotoxin decreased TNF-alpha gene expression and protein production by RAW-264.7 mouse macrophage-like cells stimulated with lipopolysaccharide. In vivo, gliotoxin treatment of mice was begun on day 3 of 5% DSS application dissolved in the drinking water and continued until day 8. Gliotoxin treatment dose-dependently down-regulated colonic inflammation as assessed histologically and in parallel there was a suppression of colonic TNF-alpha and IL-1 alpha mRNA expression on day 8 as analysed by semiquantitative reverse transcriptase-polymerase chain reaction (P < 0.01). Furthermore, colonic NF-kappa B DNA-binding activity was increased in DSS-induced colitis and was suppressed by gliotoxin. These results demonstrate the essential role of NF-kappa B in DSS-induced colitis and indicate a molecular approach to the treatment of intestinal inflammatory disorders.

Item Type: Article
Uncontrolled Keywords: BOWEL-DISEASE; TRANSCRIPTION FACTOR; EPITHELIAL-CELLS; ULCERATIVE-COLITIS; ADHESION MOLECULES; CROHNS-DISEASE; EXPRESSION; METABOLITE; MUCOSA; EPIPOLYTHIODIOXOPIPERAZINES; DSS-colitis; NF-kappa B; gliotoxin
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 17 May 2022 08:23
Last Modified: 17 May 2022 08:23
URI: https://pred.uni-regensburg.de/id/eprint/42611

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