Intrinsic renal cells are the major source of interleukin-1 beta synthesis in normal and diseased rat kidney
Intrinsic renal cells are the major source of interleukin-1 beta synthesis in normal and diseased rat kidney
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DOI：
10.1093/ndt/12.6.1109
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发表时间：
1997-06-01
影响因子：
6.1
通讯作者：
NikolicPaterson, DJ
中科院分区：
文献类型：
--
作者：
Tesch, GH;Yang, N;NikolicPaterson, DJ
背景许多研究已经证明了白细胞介素-1（IL-1）在肾小球肾炎实验模型中的病理作用，但肾脏IL-1产生的细胞模式仍不清楚。因此，本研究的目的是鉴定正常和患病大鼠肾脏中表达IL-1的细胞类型。采用北方印迹法、原位杂交和免疫组化双标法检测了正常大鼠和加速性抗GEM肾炎大鼠肾组织中IL-1 β的表达。通过北方印迹分析和原位杂交，可以很容易地检测到正常大鼠肾脏中白细胞介素-1 β mRNA的表达。免疫组织化学染色显示肾小球内皮细胞和皮质肾小管上皮细胞组成性表达IL-1 β。在大鼠抗GBM肾小球肾炎中，全肾IL-1 β mRNA显著增加。肾小球IL-1 β免疫染色上调，由足细胞、系膜细胞和浸润的巨噬细胞表达，并且在肾小球新月体中特别突出。ED 1抗体的双重染色显示，高达13%的肾小球巨噬细胞表达IL-1 β，而新月体内48%的巨噬细胞对IL-1 β染色。然而，在皮质肾小管上皮细胞中观察到IL-1 β表达的最显著增加，特别是在肾小管损伤区域。原位杂交证实肾小管IL-1 β染色是由于局部细胞因子的合成而不是蛋白吸收。本研究已经确定了正常大鼠肾脏中肾小球内皮细胞和肾小管上皮细胞的组成性IL-1 β表达。此外，在大鼠抗GEM疾病中，内源性肾小球细胞和肾小管的IL-1 β表达显著上调，表明这些细胞在IL-1依赖性新月体形成和肾小管间质损伤中发挥重要作用。
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-GEM 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-GEM disease suggests an important role for these cells in IL-1 dependent crescent formation and tubulointerstitial injury.