title: Characterization of CCL19 and CCL21 in rheumatoid arthritis.
abstract: OBJECTIVE
  To characterize the expression of CCL19 and CCL21 in rheumatoid arthritis (RA) synovial tissue (ST) and to examine their regulation and pathogenetic role in macrophages and RA ST fibroblasts.
  
  
  METHODS
  Expression of CCL19 and CCL21 in RA and normal ST was demonstrated by immunohistochemistry analysis. CCL19 and CCL21 levels in synovial fluid (SF) from patients with osteoarthritis (OA), juvenile idiopathic arthritis, psoriatic arthritis (PsA), and RA were quantified by enzyme-linked immunosorbent assay (ELISA). Regulation of CCL19 and CCL21 expression in in vitro-differentiated RA peripheral blood macrophages as well as RA ST fibroblasts was determined by real-time reverse transcription-polymerase chain reaction. Proangiogenic factor production in CCL19- and CCL21-activated in vitro-differentiated peripheral blood macrophages and RA ST fibroblasts was examined by ELISA.
  
  
  RESULTS
  CCL19 and CCL21 were elevated in RA ST compared to tissue from normal controls. Levels of CCL19 and CCL21 were greatly increased in RA and PsA SF versus OA SF. In RA macrophages and fibroblasts, expression of CCL19 was increased by stimulation with lipopolysaccharide, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β). However, CCL21 expression was modulated only by IL-1β in RA fibroblasts, and by TNFα and RA SF in RA macrophages. CCL19 and CCL21 activation induced vascular endothelial growth factor and angiotensin I (Ang I) production in RA ST fibroblasts and secretion of IL-8 and Ang I from macrophages.
  
  
  CONCLUSIONS
  The findings of the present study identify, for the first time, regulators of CCL19 and CCL21 in RA fibroblasts and in vitro-differentiated RA peripheral blood macrophages and demonstrate a novel role of CCL19/CCL21 in angiogenesis in RA.
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Pickens
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Chamberlain
authors.forename: Michael V
authors.initials: MV
authors.lastname: Volin
authors.forename: Richard M
authors.initials: RM
authors.lastname: Pope
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mandelin
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahrara
mesh_terms: D001171:Arthritis, Juvenile / Q000378:metabolism / Q000473:pathology; D015535:Arthritis, Psoriatic / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000378:metabolism*; D054421:Chemokine CCL21 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054415:Chemokine CCL19; D054421:Chemokine CCL21; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha