title: Activation of the transcription factor nuclear factor-kappaB in human inflamed synovial tissue.
abstract: OBJECTIVE
  The transcription factor nuclear factor kappaB (NF-kappaB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF-kappaB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis.
  
  
  METHODS
  Immunohistochemical staining was performed using both polyclonal and monoclonal "activity-specific" antibodies to the Rel-A (p65) subunit of NF-kappaB (anti-Rel-A nuclear location sequences). Histologic features of inflammation were also scored.
  
  
  RESULTS
  Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining.
  
  
  CONCLUSIONS
  The activation of NF-kappaB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.
authors.affiliation: London Hospital Medical College, University of London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Marok
authors.forename: P G
authors.initials: PG
authors.lastname: Winyard
authors.forename: A
authors.initials: A
authors.lastname: Coumbe
authors.forename: M L
authors.initials: ML
authors.lastname: Kus
authors.forename: K
authors.initials: K
authors.lastname: Gaffney
authors.forename: S
authors.initials: S
authors.lastname: Blades
authors.forename: P I
authors.initials: PI
authors.lastname: Mapp
authors.forename: C J
authors.initials: CJ
authors.lastname: Morris
authors.forename: D R
authors.initials: DR
authors.lastname: Blake
authors.forename: C
authors.initials: C
authors.lastname: Kaltschmidt
authors.forename: P A
authors.initials: PA
authors.lastname: Baeuerle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis* / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D016328:NF-kappa B