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  • Meeting abstract
  • Open Access

Inmunohistologic analysis of synovial tissue from early and late osteoarthritic patients. A potential role for COX-2 and NF-κB1 (p50) regulation in early disease

  • 1,
  • 1 and
  • 1
Arthritis Research & Therapy20024 (Suppl 1) :34

https://doi.org/10.1186/ar475

  • Received: 15 January 2002
  • Published:

Keywords

  • PGE2
  • Synovial Tissue
  • Inflammatory Cell Infiltrate
  • Parthenolide
  • Inflame Profile

Osteoarthritis (OA) is an erosive inflammatory disease originated by a biomechanical alteration that, in some patients, shows a strong component of inflammatory infiltrates in the synovial membrane resembling rheumatoid arthritis. T cells and macrophages initiate, amplify and perpetuate the inflammatory response. In stimulated cells, NF-κB, commonly formed by homodimers of NF-κB1 (p50), or heterodimers with RelA (p65) or c-Rel, bind to promoters and enhance, or occasionally inhibit, gene transcription through direct interaction with DNA. The activation of NF-κB may be a key step in the pathogenesis of OA. Inducible cyclooxygenase (COX-2) may also play a role in the inflamed profile, since it has a κB motive in its promoter. The aim of this study is to evaluate the differences in OA tissue, focusing on whether the pattern of NF-κB activation is quantitatively different in early and late stages, and its effect in COX-2 expression. Additional in vitro experiments, using OA cultured cells, were performed to evaluate the role of IL-6 and PGE2 in NF-κB activation and COX-2 induction. A significant increase in inflammatory cell infiltrate and hyperplasia of synovium was a feature found in early OA tissue. NF-κB1 and RelA were detected in all the OA samples studied, with significant increases observed in early OA tissue (P = 0.006 and P = 0.012). In concordance with NF-κB1/RelA, COX-2 expression was increased in early OA. Activation of p50 and p65 subunits of NF-κB showed a positive correlation with COX-2 (r = 0.6169 and r = 0.6620, respectively) and inverse correlation with COX-1 (r=-0.627 and r=-0.858) in early OA tissue, while only a positive correlation was observed between p50 and COX-2 in late OA (r = 0.4129). In vitro synoviocytes cell cultures the activation of NF-κB in cells was observed together with an increase in COX-2 production. This activation was inhibited by parthenolide, an inhibitor of IκB degradation, and a concomitant decrease in COX-2 protein was observed as a result of the NF-κB inhibition. These findings support the conclusion that NF-κB and COX-2 play an important role in the early stages of OA, and specific inhibition could be a strategic approach in early OA.

Authors’ Affiliations

(1)
St Vincent's Hospital, Dublin, Ireland

Copyright

© BioMed Central Ltd 2002

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