title: Proteasome inhibitor bortezomib suppresses nuclear factor-kappa B activation and ameliorates eye inflammation in experimental autoimmune uveitis.
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.
authors: Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, No. 35, Siao-Dong Road, Tainan 70403, Taiwan ; Department of Ophthalmology, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors: Sheng-Min
authors: SM
authors: Hsu
authors: Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors: Chang-Hao
authors: CH
authors: Yang
authors: Department of Microbiology and Immunology, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan.
authors: Fang-Hsiu
authors: FH
authors: Shen
authors: Department of Microbiology and Immunology, College of Medicine, National Cheng-Kung University, Tainan 70101, Taiwan.
authors: Shun-Hua
authors: SH
authors: Chen
authors: Department of Ophthalmology, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors: Chia-Jhen
authors: CJ
authors: Lin
authors: Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University, No. 35, Siao-Dong Road, Tainan 70403, Taiwan ; Department of Pediatrics, National Cheng-Kung University Hospital, Tainan 70403, Taiwan.
authors: Chi-Chang
authors: CC
authors: Shieh
mesh_terms: D000818:Animals; D000069286:Bortezomib / Q000008:administration & dosage / Q000627:therapeutic use*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D061988:Proteasome Inhibitors; D000069286:Bortezomib
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