Gliotoxin Protects Against TNBS-induced Colitis Via Down-regulation of NF B Activation / 대한해부학회지

ABSTRACT

During inflammation of the colon, cells of the gut mucosa express numerous inflammatory mediators including interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta(IL-1beta). These cytokines have been implicated as contributing factors in the inflammatory process, which may result in colitis during inflammatory bowel disease (IBD). Gliotoxin is a fungal metabolite of an epipolythiodioxopiperazine analogue with immunosup-pressive properties in vivo and in vitro, but the effects of gliotoxin on IBD have not been largely evaluated. Therefore, this study evaluated the potential of gliotoxin to protect against TNBS-induced colitis. One microgram of gliotoxin in 100microliter of vehicle was intra-rectally administered into mice exhibiting trinitrobenzene sulfonic acid (TNBS)-induced colitis. IL-8 secretion was measured using an enzyme-linked immu-nosorbent assay (ELISA), myeloperoxidase (MPO) activity was evaluated spectrophotometically, and IkappaB degradation was analyzed on Western blots. Gliotoxin treatment of mice bearing TNBS-induced colitis improved macro-and micro-pathological findings and dramatically decreased MPO activity, a marker of leukocyte infiltration. Furthermore, gliotoxin decreased IkappaB degradation and IL-8 induction caused by TNF-alpha or IL-1beta in HT-29 cells. These findings suggest that gliotoxin partially protects against TNBS-induced colitis through the sup-pression of IL-8 induction and IkappaB degradation by inflammatory mediators such as TNF-alpha or IL-1beta.