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Bortezomib attenuates murine collagen-induced arthritis

 S-W Lee  ;  J-H Kim  ;  Y-B Park  ;  S-K Lee 
 ANNALS OF THE RHEUMATIC DISEASES, Vol.68(11) : 1761-1767, 2009 
Journal Title
Issue Date
Animals ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/therapeutic use* ; Antirheumatic Agents/toxicity ; Arthritis, Experimental/diagnostic imaging ; Arthritis, Experimental/drug therapy* ; Arthritis, Experimental/pathology ; Boronic Acids/administration & dosage ; Boronic Acids/therapeutic use* ; Boronic Acids/toxicity ; Bortezomib ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/methods ; Inflammation Mediators/metabolism ; Male ; Mice ; Mice, Inbred DBA ; Protease Inhibitors/administration & dosage ; Protease Inhibitors/therapeutic use* ; Protease Inhibitors/toxicity ; Pyrazines/administration & dosage ; Pyrazines/therapeutic use* ; Pyrazines/toxicity ; Severity of Illness Index ; Treatment Outcome ; X-Ray Microtomography
OBJECTIVES: Nuclear factor kappa B (NF-kappaB) is a major regulator of pivotal proinflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA). Bortezomib inhibits NF-kappaB activation by blocking the degradation of the NF-kappaB inhibitor, I-kappaB. In this study, the efficacy of bortezomib on murine collagen-induced arthritis (CIA) was investigated. METHODS: Thirty-five male DBA/1 mice were divided into five groups. All mice except controls were injected with type II collagen. Mice in the bortezomib-treated groups were injected intraperitoneally with 0.01, 0.1 and 1 mg/kg bortezomib twice a week for 2 weeks. Controls and mice in the untreated group were also injected intraperitoneally with phosphate-buffered saline in the same manner. Arthritis score and paw thickness were measured and histopathological assessment of joint sections was performed. The expression of proinflammatory cytokines and enzymes was evaluated by immunohistochemical staining. Joint destruction was confirmed using three-dimensional micro-computerised tomography (CT). Blood cells were counted and liver and kidney functions were monitored. RESULTS: Bortezomib significantly attenuated the severity of arthritis and histopathological findings in CIA mice. The expression of tumour necrosis factor alpha, IL-1beta, IL-6, matrix metalloproteinase 3, cyclooxygenase 2 and inducible nitric oxide synthase decreased in bortezomib-treated mice compared with untreated mice. In addition, micro-CT confirmed that bortezomib reduced joint destruction. No adverse effects in blood cells, liver or kidneys were observed with bortezomib treatment. CONCLUSIONS: These data suggest that bortezomib may play an anti-inflammatory role in the pathophysiology of RA and serve as a new therapeutic modality for RA.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
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