Intrinsic renal cells are the major source of interleukin-1β 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-1β 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-1β mRNA expression was readily detectable in normal rat kidney by northern blot analysis and in situ hybridization. Immunohistochemistry staining demonstrated constitutive IL-1β expression by glomerular endothelial cells and cortical tubular epithelial cells. There was a marked increase in whole kidney IL-1β mRNA in rat anti-GBM glomerulonephritis. Glomerular IL-1β 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-1β expression in up to 13% of glomerular macrophages, whereas 48% of macrophages within crescents stained for IL-1β. However, the most marked increase in IL-1β expression was seen in cortical tubular epithelial cells, particularly in areas of tubular damage. In situ hybridization confirmed that tubular IL-1β staining was due to local cytokine synthesis rather than protein absorption. Conclusions. This study has identified constitutive IL-1β expression by glomerular endothelium and tubular epithelial cells in normal rat kidney. In addition, the marked upregulation of IL-1β 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.