Bortezomib attenuates murine collagen-induced arthritis

S. W. Lee, J. H. Kim, Y. B. Park, S. K. Lee

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Objectives: Nuclear factor kappa B (NF-κB) is a major regulator of pivotal proinflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA). Bortezomib inhibits NF-κB activation by blocking the degradation of the NF-κB inhibitor, I-κB. 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-1β, IL-6, matrix metalloproteinase 3, cyclooxygenase 2 and inducible nitric oxide synthase decreased in bortezomibtreated 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.

Original languageEnglish
Pages (from-to)1761-1767
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume68
Issue number11
DOIs
Publication statusPublished - 2009 Nov

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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