title: High mobility group box chromosomal protein 1: a novel proinflammatory mediator in synovitis.
abstract: OBJECTIVE
  High mobility group box chromosomal protein 1 (HMGB-1) is a ubiquitous chromatin component expressed in nucleated mammalian cells. It has recently and unexpectedly been demonstrated that stimulated live mononuclear phagocytes secrete HMGB-1, which then acts as a potent factor that causes inflammation and protease activation. Macrophages play pivotal roles in the pathogenesis of arthritis. The aim of this study was to determine whether synovial macrophage expression of HMGB-1 is altered in human and experimental synovitis.
  
  
  METHODS
  Intraarticular tissue specimens were obtained from healthy Lewis rats, Lewis rats with Mycobacterium tuberculosis-induced adjuvant arthritis, and from patients with rheumatoid arthritis (RA). Specimens were immunohistochemically stained for cellular HMGB-1. Extracellular HMGB-1 levels were assessed in synovial fluid samples from RA patients by Western blotting.
  
  
  RESULTS
  Immunostaining of specimens from normal rats showed that HMGB-1 was primarily confined to the nucleus of synoviocytes and chondrocytes, with occasional cytoplasmic staining and no extracellular matrix deposition. In contrast, inflammatory synovial tissue from rats with experimental arthritis as well as from humans with RA showed a distinctly different HMGB-1 staining pattern. Nuclear HMGB-1 expression was accompanied by a cytoplasmic staining in many mononuclear cells, with a macrophage-like appearance and an extracellular matrix deposition. Analysis of synovial fluid samples from RA patients further confirmed the extracellular presence of HMGB-1; 14 of 15 samples had HMGB-1 concentrations of 1.8-10.4 microg/ml.
  
  
  CONCLUSIONS
  The proinflammatory mediator HMGB-1 was abundantly expressed as a nuclear, cytoplasmic, and extracellular component in synovial tissues from RA patients and from rats with experimental arthritis. These findings suggest a pathogenetic role for HMGB-1 in synovitis and indicate a new potential therapeutic target molecule.
authors.affiliation: Rheumatology Research Unit, Karolinska Hospital, Stockholm 171 76, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Kokkola
authors.forename: E
authors.initials: E
authors.lastname: Sundberg
authors.forename: A-K
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: K
authors.initials: K
authors.lastname: Palmblad
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Ulloa
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: X-J
authors.initials: XJ
authors.lastname: Yan
authors.forename: R
authors.initials: R
authors.lastname: Furie
authors.forename: N
authors.initials: N
authors.lastname: Chiorazzi
authors.forename: K J
authors.initials: KJ
authors.lastname: Tracey
authors.forename: U
authors.initials: U
authors.lastname: Andersson
authors.forename: H Erlandsson
authors.initials: HE
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D013585:Synovitis / Q000276:immunology / Q000473:pathology
chemical_list: D024243:HMGB1 Protein; D018836:Inflammation Mediators