Treatment with N-tosyl-l-phenylalanine chloromethyl ketone after the onset of collagen-induced arthritis reduces joint erosion and NF-κB activation

Jin Choi, Kyung Ho Ha, Mi Sun Byun, So Youn Min, Min Jung Park, Hyun Sil Park, Hye Joa Oh, Ji Hyeon Ju, Ho Youn Kim, Dae Myung Jue

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) is known to inhibit NF-κB activation and the expression of inflammation mediators in cultured cells. We measured the potential of TPCK to inhibit the pathogenesis of collagen-induced arthritis by blocking NF-κB activation. Arthritis was induced in DBA/1J mice by the injection of bovine type II collagen in adjuvant on days 0 and 14. Mice received either TPCK (3 or 10 mg/kg, i.p.) or vehicle three times a week for 3 weeks starting on day 21. TPCK moderately reduced clinical disease activity scores, whereas it markedly suppressed histological indications of joint destruction. In vitro production of tumor necrosis factor-α, interleukin-6, and monocyte chemotactic protein-1 from lipopolysaccharide-stimulated spleen cells was also reduced by in vivo treatment with TPCK. Proliferation of cells isolated from spleen or draining lymph nodes and production of interferon-γ and interleukin-17 in response to stimulation with type II collagen was decreased by TPCK. Moreover, nuclear NF-κB activity induced by collagen immunization was significantly reduced in mice treated with TPCK. Finally, osteoclast differentiation of bone marrow cells induced by macrophage colony-stimulating factor and receptor activator of NF-κB ligand was completely inhibited by TPCK. These results indicate that TPCK attenuates collagen-induced arthritis and bone erosion by suppressing NF-κB activation and thus expression of inflammatory and osteoclastogenic genes.

Original languageEnglish (US)
Pages (from-to)108-113
Number of pages6
JournalEuropean Journal of Pharmacology
Volume595
Issue number1-3
DOIs
StatePublished - Oct 24 2008

Keywords

  • Collagen-induced arthritis
  • Cytokine
  • Inflammation
  • NF-κB
  • Rheumatoid arthritis
  • Tosylphenylalanyl chloromethyl ketone

ASJC Scopus subject areas

  • Pharmacology

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