Induction of heat shock protein 70 inhibits tumor necrosis factor α-induced lipid peroxidation in rat mesangial cells

Abstract

Monocyte/macrophage infiltration is the well known initial features associated with the development of glomerular disease including non-immune mediated nephropathy. Tumor necrosis factor α(TNFα), a cytokine produced primarily by monocyte/macrophage, exhibits similar effects as observed at the initial stages and during the progression of glomerular injury. Because the mesangial cells are target cells for glomerular injury, the present study examined the effect of TNFα on glomerular mesaigial cell membrane lipid peroxidation ´as an index of cytotoxicity attributing to TNFα. Primary culture of rat mesangial cell was established by incubation of glomeruli isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method: The levels of lipid peroxides in the mesangial cells were quantitated by malondialdehyde- thiobarbituric acid adduct formation. During an 8 hour incubation at 37℃, TNFα at 10 to 10,000 units/ml increased the levels of lipid peroxides dose dependently. Western blot analysis demonstrated that a short thermal stress induced heat shock response and the synthesis of heat shock protein 70(hsp70) in this mesangial cells. Further, this induction of hsp 70 prevented increase of lipid peroxides in the mesangial cells exposed to TNFα. These data suggest that TNFα-induced lipid peroxidation in the mesangial cells may have pathophysiological relevance to glomerular injury and prior induction of heat shock response may play a role in the cellular resistance against TNFα-induced glomerular injury.