Ulcerative colitis is an inflammatory bowel Z-VAD-FMK Caspase inhibitor disease characterized by pathologic mucosal damage and ulceration, which can involve the rectum and extend proximally. Although its etiology and pathogenesis have not yet been identified, inappropriate activation of the mucosal immune system has been found to play an important role in mucosal inflammation. At sites of intestinal inflammation, granulocytes and macrophages produce high levels of pro-inflammatory cytokines, including interleukin -1b, IL-6, and tumor necrosis factor -a, which are directly involved in the pathogenesis of ulcerative colitis. The oral administration of dextran sulfate sodiumsolution to rodents is widely employed as a model of human ulcerative colitis, because it causes acute inflammatory reactions and ulceration in the entire colon similar to that observed in patients. Mice exposed to DSS in drinking water develop inflammation only in the large intestine and show signs such as diarrhea, hematochezia, and body weight loss with histologic findings including inflammatory cell infiltration, erosion, ulceration, and crypt abscesses. Furthermore, increased production of pro-inflammatory cytokines, including interferon – c, TNF-a, IL-1, IL-6, IL-12, and IL-17, has been found in the colon of mice with DSS-induced colitis. The major intracellular pathway for protein degradation is the ubiquitin-proteasome pathway. Proteasomes are large multimeric protease complexes located in both the cytoplasm and nuclei that selectively and timely degrade most cellular proteins. The 26S proteasome consists of a central 20S core and two 19S regulatory complexes. Upon Silmitasertib stimulation, the formation of immunoproteasomes is induced. The ubiquitination of target proteins is an important mechanism for the discriminatory nature of protein degradation by proteasomes. Proteasome inhibitors have received much attention because of their potent anti-tumor activity. In particular, bortezomib, a boronic acid dipeptide derivative, is a specific protease inhibitor that has recently been approved for the treatment of 
relapsed multiple myeloma, a plasma cell neoplasia, because of its direct growth-inhibitory and apoptotic effects on this cancer. Furthermore, bortezomib is effective in the treatment of allograft rejection, graft-versus-host disease, contact hypersensitivity responses, and lupus-like disease in mice. Proteasome inhibitors induce apoptosis in activated and proliferating, but not resting, T cells, suggesting one possible mechanism for the suppression of T cell-mediated immune responses by bortezomib. In this study, the effect of bortezomib in ulcerative colitis was examined using DSS-induced mouse colitis. We treated mice twice weekly with bortezomib or phosphate buffered salinecontrol starting 2 days before DSS administration. DAI scores were based on weight loss, stool consistency, and bleeding. Statistically significant body weight loss was first observed in DSS-treated mice on day 6. Bortezomib treatment significantly attenuated body weight loss compared with controltreated mice and delayed the increase in DAI scores by 1 day from day 4to day 5. DAI scores were also significantly higher in bortezomib-treated mice than in control-treated mice from day 5�C7. Each element of the DAI score showed the same trend as the overall DAI score, suggesting that bortezomib treatment suppressed DSS-induced colitis in mice. The results of this study demonstrate that bortezomib treatment inhibits DSS-induced colitis in mice. The suppression of DSS-induced colitis by bortezomib treatment correlated with a decrease in CD4 + and CD8 + T cell accumulation both in the colon and mesenteric lymph nodes.