Proteasome Inhibitor Bortezomib Suppresses Nuclear Factor-Kappa B Activation and Ameliorates Eye Inflammation in Experimental Autoimmune Uveitis. (12th January 2015)

• Record Type: Journal Article
• Authors: Hsu, Sheng-Min; Yang, Chang-Hao; Shen, Fang-Hsiu; Chen, Shun-Hua; Lin, Chia-Jhen; Shieh, Chi-Chang
• Other Names: Grzybowski Andrzej Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2015(2015)
• Publication Date: 2015-01-12
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2015/847373
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : Bortezomib is a proteasome inhibitor used for hematologic cancer treatment. Since it can suppress NF- κ B 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- κ B 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- κ B was suppressed and expression of several key inflammatory mediators including TNF- α, IL-1 α, IL-1 β, 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.