proteasome inhibitor bortezomib suppresses nuclear factor-kappa b activation and ameliorates eye inflammation in experimental autoimmune uveitis
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2015
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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.
| Reference Key |
hsu2015mediatorsproteasome
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|---|---|
| Authors | ;Sheng-Min Hsu;Chang-Hao Yang;Fang-Hsiu Shen;Shun-Hua Chen;Chia-Jhen Lin;Chi-Chang Shieh |
| Journal | polyhedron |
| Year | 2015 |
| DOI |
10.1155/2015/847373
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| URL | |
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