Increased synovial tissue NF-κB1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis

Maria J. Benito, Eithne Murphy, Evelyn P. Murphy, Wim B. Van Den Berg, Oliver FitzGerald, Barry Bresnihan

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To compare the expression of the Rel/NF-κB subunits, NF-κB1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. Methods. Synovial tissue was selected at arthroscopy from sites adjacent to the CPJ and from the suprapatellar pouch of patients who were referred to an early arthritis clinic. Tissue samples from patients with osteoarthritis (OA) undergoing knee arthroplasty were also studied. Rel/NF-κB subunit activation and expression were measured by electrophoretic mobility shift assay and supershift analyses and by immunohistochemistry. Results. Tissue samples were obtained from 10 patients with rheumatoid arthritis (RA), 7 with a seronegative arthropathy (SnA), and 6 with OA. Rel/NF-κB was abundantly expressed in all samples. In both RA and SnA synovial tissue, the absolute number of NF-κB1+ cells at the CPJ was significantly higher than at non-CPJ sites (P = 0.006 and P = 0.02, respectively). The proportion of cells expressing NF-κB1 was also significantly higher at the CPJ compared with non-CPJ sites (P = 0.003 in RA, P = 0.009 in SnA). The numbers of RelA+ cells were consistently lower throughout. In RA synovial tissue, but not in SnA synovial tissue, both the absolute number and the proportion of RelA+ cells were significantly higher at the CPJ than at non-CPJ sites (P = 0.003 and P = 0.01, respectively). In OA synovial tissue, the numbers of cells expressing NF-κB1 and RelA were similar to those observed at the non-CPJ sites in all inflammatory tissues studied. Conclusion. In this study of early inflammatory arthritis, expression of NF-κB1 in synovial tissue was highest at sites most likely to be associated with joint erosion. These observations are consistent with a critical role of NF-κB1 in joint destruction, and support the rationale for specific therapeutic inhibition of NF-κB in RA.

Original languageEnglish
Pages (from-to)1781-1787
Number of pages7
JournalArthritis and Rheumatism
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 2004
Externally publishedYes

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