title: Intrinsic renal cells are the major source of interleukin-1 beta synthesis in normal and diseased rat kidney.
abstract: BACKGROUND
  A number of studies have demonstrated a pathological role for interleukin-1 (IL-1) in experimental models of glomerulonephritis, but the cellular pattern of renal IL-1 production remains poorly characterized. The aim of this study, therefore, was to identify the cell types expressing IL-1 in normal and diseased rat kidney.
  
  
  METHODS
  Renal IL-1 beta expression was examined in normal rats and during a 21-day time course of rat accelerated anti-GBM glomerulonephritis by northern blotting, in situ hybridization and double immunohistochemistry.
  
  
  RESULTS
  Interleukin-1 beta mRNA expression was readily detectable in normal rat kidney by northern blot analysis and in situ hybridization. Immunohistochemistry staining demonstrated constitutive IL-1 beta expression by glomerular endothelial cells and cortical tubular epithelial cells. There was a marked increase in whole kidney IL-1 beta mRNA in rat anti-GBM glomerulonephritis. Glomerular IL-1 beta immunostaining was upregulated, being expressed by podocytes, mesangial cells and infiltrating macrophages, and was particularly prominent within glomerular crescents. Double staining with the ED1 antibody showed IL-1 beta expression in up to 13% of glomerular macrophages, whereas 48% of macrophages within crescents stained for IL-1 beta. However, the most marked increase in IL-1 beta expression was seen in cortical tubular epithelial cells, particularly in areas of tubular damage. In situ hybridization confirmed that tubular IL-1 beta staining was due to local cytokine synthesis rather than protein absorption.
  
  
  CONCLUSIONS
  This study has identified constitutive IL-1 beta expression by glomerular endothelium and tubular epithelial cells in normal rat kidney. In addition, the marked upregulation of IL-1 beta expression by intrinsic glomerular cells and tubules in rat anti-GBM disease suggests an important role for these cells in IL-1 dependent crescent formation and tubulointerstitial injury.
authors.affiliation: Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: G H
authors.initials: GH
authors.lastname: Tesch
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
authors.forename: R
authors.initials: R
authors.lastname: Foti
authors.forename: S J
authors.initials: SJ
authors.lastname: Chadban
authors.forename: R C
authors.initials: RC
authors.lastname: Atkins
authors.forename: D J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004727:Endothelium / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger