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Nephrology Dialysis Transplantation, Vol 14, Issue 90001 35-38, Copyright © 1999 by Oxford University Press

ORIGINAL ARTICLES

Adoptive transfer of genetically modified macrophages elucidated TGF-{beta}-mediated 'self-defence' of the glomerulus against local action of macrophages

M Kitamura
Glomerular Bioengineering Unit, Department of Medicine, University College London Medical School, The Rayne Institute, 5 University Street, London WC1E 6JJ, UK

TGF-{beta} has several anti-inflammatory properties which may be relevant to prevention of or recovery from acute glomerular inflammation. Using genetically modified mesangial cells and a technique for in vivo macrophage transfer, this article provides evidence for TGF-{beta}-mediated 'self-defence' of the glomerulus against macrophages. Rat mesangial cells stably transfected with TGF-{beta}1 showed a blunted response to the macrophage-derived, proinflammatory cytokine IL-1{beta}. In contrast, mesangial cells expressing the dominant-interfering TGF-{beta} receptor showed an enhanced response to IL-1. Similarly, externally added TGF-{beta}1 inhibited the cytokine response of normal glomeruli, and isolated nephritic glomeruli producing active TGF-{beta}1 showed a depressed response to IL-1{beta}, compared to normal glomeruli. Consistent with these in vitro results, in vivo transfer of activated macrophages revealed that the TGF-{beta}-producing glomeruli are insensitive to the effector action of macrophages. These results indicate that TGF-{beta}1 functions as an endogenous 'defender' that counteracts local action of activated macrophages in the glomerulus.
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