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Mediators of Inflammation
Volume 2015 (2015), Article ID 847373, 10 pages
http://dx.doi.org/10.1155/2015/847373
Research Article

Proteasome Inhibitor Bortezomib Suppresses Nuclear Factor-Kappa B Activation and Ameliorates Eye Inflammation in Experimental Autoimmune Uveitis

1Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, No. 35, Siao-Dong Road, Tainan 70403, Taiwan
2Department of Ophthalmology, National Cheng-Kung University Hospital, Tainan 70403, Taiwan
3Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, Taiwan
4Department of Microbiology and Immunology, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan
5Department of Pediatrics, National Cheng-Kung University Hospital, Tainan 70403, Taiwan

Received 16 May 2014; Revised 5 September 2014; Accepted 7 September 2014

Academic Editor: Andrzej Grzybowski

Copyright © 2015 Sheng-Min Hsu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.