title: IL-17 Expression in the Time Course of Acute Anti-Thy1 Glomerulonephritis.
abstract: BACKGROUND
  Interleukin-17 (IL-17) is a new pro-inflammatory cytokine involved in immune response and inflammatory disease. The main source of IL-17 is a subset of CD4+ T-helper cells, but is also secreted by non-immune cells. The present study analyzes expression of IL-17 in the time course of acute anti-thy1 glomerulonephritis and the role of IL-17 as a potential link between inflammation and fibrosis.
  
  
  METHODS
  Anti-thy1 glomerulonephritis was induced into male Wistar rats by OX-7 antibody injection. After that, samples were taken on days 1, 5, 10 (matrix expansion phase), 15 and 20 (resolution phase). PBS-injected animals served as controls. Proteinuria and histological matrixes score served as the main markers for disease severity. In in vitro experiments, NRK-52E cells were used. For cytokine expressions, mRNA and protein levels were analyzed by utilizing RT-PCR, in situ hybridization and immunofluorescence.
  
  
  RESULTS
  Highest IL-17 mRNA-expression (6.50-fold vs. con; p<0.05) was found on day 5 after induction of anti-thy1 glomerulonephritis along the maximum levels of proteinuria (113 ± 13 mg/d; p<0.001), histological glomerular-matrix accumulation (82%; p<0.001) and TGF-β1 (2.2-fold; p<0.05), IL-6 mRNA expression (36-fold; p<0.05). IL-17 protein expression co-localized with the endothelial cell marker PECAM in immunofluorescence. In NRK-52E cells, co-administration of TGF-β1 and IL-6 synergistically up-regulated IL-17 mRNA 4986-fold (p<0.001).
  
  
  CONCLUSIONS
  The pro-inflammatory cytokine IL-17 is up-regulated in endothelial cells during the time course of acute anti-thy1 glomerulonephritis. In vitro, NRK-52E cells secrete IL-17 under pro-fibrotic and pro-inflammatory conditions.
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Loof
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.|German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Krämer
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Gaedeke
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Hans-Hellmut
authors.initials: HH
authors.lastname: Neumayer
authors.affiliation: Department of Nephrology and Center of Cardiovascular Research, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism*; D015850:Interleukin-6 / Q000008:administration & dosage / Q000235:genetics; D007518:Isoantibodies / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C515934:Il17a protein, rat; D020381:Interleukin-17; D015850:Interleukin-6; D007518:Isoantibodies; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C035678:anti-Thy antibody