Proteasome Inhibitor Bortezomib Ameliorates Intestinal Injury in MiceReportar como inadecuado




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Background

Bortezomib is a proteasome inhibitor that has shown impressive efficacy in the treatment of multiple myeloma. In mice, the addition of dextran sulfate sodium DSS to drinking water leads to acute colitis that can serve as an experimental animal model for human ulcerative colitis.

Methodology-Principal Findings

Bortezomib treatment was shown to potently inhibit murine DSS-induced colitis. The attenuation of DSS-induced colitis was associated with decreased inflammatory cell infiltration in the colon. Specifically, bortezomib-treated mice showed significantly decreased numbers of CD4+ and CD8+ T cells in the colon and mesenteric lymph nodes. Bortezomib treatment significantly diminished interferon IFN-γ expression in the colon and mesenteric lymph nodes. Furthermore, cytoplasmic IFN-γ production by CD4+ and CD8+ T cells in mesenteric lymph nodes was substantially decreased by bortezomib treatment. Notably, bortezomib enhanced T cell apoptosis by inhibiting nuclear factor-κB activation during DSS-induced colitis.

Conclusions-Significance

Bortezomib treatment is likely to induce T cell death, thereby suppressing DSS-induced colitis by reducing IFN-γ production.



Autor: Koichi Yanaba , Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi Sato

Fuente: http://plos.srce.hr/



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