Proteasome inhibitor bortezomib suppresses nuclear factor-kappa b activation and ameliorates eye inflammation in experimental autoimmune uveitis

Sheng-Min Hsu, Chang Hao Yang, Fang Hsiu Shen, Shun-hua Chen, Chia Jhen Lin, Chi-Chang Shieh

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11 Citations (Scopus)

Abstract

Bortezomib is a proteasome inhibitor used for hematologic cancer treatment. Since it can suppress NF-κB activation, which is critical for the inflammatory process, bortezomib has been found to possess anti-inflammatory activity. In this study, we evaluated the effect of bortezomib on experimental autoimmune uveitis (EAU) in mice and investigated the potential mechanisms related to NF-κB inactivation. High-dose bortezomib (0.75 mg/kg), low-dose bortezomib (0.15 mg/kg), or phosphate buffered saline was given after EAU induction. We found that the EAU is ameliorated by high-dose bortezomib treatment when compared with low-dose bortezomib or PBS treatment. The DNA-binding activity of NF-κB was suppressed and expression of several key inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-12, IL-17, and MCP-1 was lowered in the high-dose bortezomib-treated group. These results suggest that proteasome inhibition is a promising treatment strategy for autoimmune uveitis.

Original languageEnglish
Article number847373
JournalMediators of Inflammation
Volume2015
DOIs
Publication statusPublished - 2015 Jan 12

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology

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