Nephrology Dialysis Transplantation, Vol 12, Issue 6 1109-1115, Copyright © 1997 by Oxford University Press
G Tesch, N Yang, H Yu, H Lan, R Foti, S Chadban, R Atkins and D Nikolic-Paterson
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 had 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.
Keywords: crescent formation; endothelium;
glomerulonephritis; interleukin-1{beta}; macrophages; tubules
ORIGINAL ARTICLES
Intrinsic renal cells are the major source of interleukin-1{beta} synthesis in normal and diseased rat kidney
Department of Nephrology, Monash Medical Centre, Clayton Road, Clayton, Victoria 3168, Australia; Corresponding author
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