title: Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.
abstract: OBJECTIVE
  To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (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-kappa B 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-kappa B was abundantly expressed in all samples. In both RA and SnA synovial tissue, the absolute number of NF-kappa B1+ 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-kappa B1 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-kappa B1 and RelA were similar to those observed at the non-CPJ sites in all inflammatory tissues studied.
  
  
  CONCLUSIONS
  In this study of early inflammatory arthritis, expression of NF-kappa B1 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-kappa B1 in joint destruction, and support the rationale for specific therapeutic inhibition of NF-kappa B in RA.
authors.affiliation: St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Benito
authors.forename: Eithne
authors.initials: E
authors.lastname: Murphy
authors.forename: Evelyn P
authors.initials: EP
authors.lastname: Murphy
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Oliver
authors.initials: O
authors.lastname: FitzGerald
authors.forename: Barry
authors.initials: B
authors.lastname: Bresnihan
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D002356:Cartilage / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology*; D051996:Transcription Factor RelA
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D051996:Transcription Factor RelA