title: Characterization of interleukin-7 and interleukin-7 receptor in the pathogenesis of rheumatoid arthritis.
abstract: OBJECTIVE
  To characterize the expression of interleukin-7 (IL-7) and IL-7 receptor (IL-7R) in rheumatoid arthritis (RA) synovial tissue and to examine their regulation and pathogenic role in macrophages, endothelial cells, and synovial tissue fibroblasts in RA.
  
  
  METHODS
  Expression of IL-7 and IL-7R in RA and normal synovial tissue was demonstrated by immunohistochemistry. Expression and regulation of IL-7 and IL-7R in RA peripheral blood in vitro-differentiated macrophages, RA synovial tissue fibroblasts, and human microvascular endothelial cells (HMVECs) were determined by real-time reverse transcription-polymerase chain reaction and/or flow cytometry. Enzyme-linked immunosorbent assay was used to examine production of proangiogenic factors by IL-7-activated macrophages, RA fibroblasts, and endothelial cells.
  
  
  RESULTS
  IL-7 and IL-7R were coexpressed on RA synovial tissue lining and sublining macrophages and endothelial cells. Expression of IL-7 and its receptor was significantly elevated in RA synovial fluid and peripheral blood macrophages as well as RA fibroblasts, compared to normal cells. Toll-like receptor 4 ligation (with lipopolysaccharide) and tumor necrosis factor α (TNFα) stimulation modulated expression of IL-7 and IL-7R on RA macrophages and HMVECs. However, in RA fibroblasts, lipopolysaccharide and TNFα activation increased expression of IL-7R only. IL-7 also mediated RA pathogenesis by inducing production of potent proangiogenic factors from macrophages and endothelial cells.
  
  
  CONCLUSIONS
  We have identified, for the first time, regulators of IL-7 and IL-7R expression in RA fibroblasts, RA peripheral blood in vitro-differentiated macrophages, and endothelial cells. Our results document a novel role of IL-7 in RA angiogenesis.
authors.affiliation: University of Illinois at Chicago, Department of Medicine, Chicago, IL 60612, 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: Nicholas E
authors.initials: NE
authors.lastname: Talarico
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mandelin
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahrara
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha