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

Abstract

TGF-β 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-β-mediated 'self-defence' of the glomerulus against macrophages. Rat mesangial cells stably transfected with TGF-β1 showed a blunted response to the macrophage-derived, proinflammatory cytokine IL-1β. In contrast, mesangial cells expressing the dominant-interfering TGF-β receptor showed an enhanced response to IL-1. Similarly, externally added TGF-β1 inhibited the cytokine response of normal glomeruli, and isolated nephritic glomeruli producing active TGF-β1 showed a depressed response to IL-1β, compared to normal glomeruli. Consistent with these in vitro results, in vivo transfer of activated macrophages revealed that the TGF-β-producing glomeruli are insensitive to the effector action of macrophages. These results indicate that TGF-β1 functions as an endogenous 'defender' that counteracts local action of activated macrophages in the glomerulus.