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Expression of cytokines and growth factors in human glomerulonephritides

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Abstract

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, from the various autocrine and paracrine mediators identified in vitro and in animal models, so far only a few have been demonstrated in selected human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodies (ANCA), an example of an acute form of GN, and mesangial IgA GN, usually a chronic form of GN, with immunocytochemistry, in situ hybridization and the polymerase chain reaction. Normal renal tissue from tumour nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrating mononuclear cells in glomeruli and in the interstitium expressed interleukin (IL)-1β, tumour necrosis factor (TNF)-α, IL-2, interferon (IFN)-γ, platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-β. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epithelial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cytokine and growth factor receptors TNF-R, IL-1R type II, IL-2R, IFN-γR and PDGFβ-R. In contrast, in mesangial IgA-GN, IL-1β, TNF-α, IFN-γ and IL-2 were usually absent in glomeruli. Mesangial expansion in this disorder was accompanied by an increased expression of PDGF, PDGFβ-R, TGF-β and IL-6 in mesangial areas. In both conditions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistry). These results demonstrate that different cytokine and growth factor patterns are expressed in the various forms of GN, and suggest that the local production of these peptides plays an important role in the pathogenesis and progression of human glomerulonephritides.

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Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, D-69120, Heidelberg, Germany

    Rüdiger Waldherr, Irene L. Noronha, Zofia Niemir, Cornelia Krüger, Henning Stein & Gariele Stumm

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  1. Rüdiger Waldherr
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  2. Irene L. Noronha
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  3. Zofia Niemir
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  4. Cornelia Krüger
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  5. Henning Stein
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  6. Gariele Stumm
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Waldherr, R., Noronha, I.L., Niemir, Z. et al. Expression of cytokines and growth factors in human glomerulonephritides. Pediatr Nephrol 7, 471–478 (1993). https://doi.org/10.1007/BF00857578

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