Methylprednisolone accelerates the resolution of glomerulonephritis by sensitizing mesangial cells to apoptosis

Glucocorticoid has long been used to treat patients with glomerulonephritis because it ameliorates mesangial cell proliferation and proteinuria, in pa rt by suppressing nuclear factor-kappa B (NF-kappaB) activation, which regu lates the transcription of various pro-inflammatory genes. Recent evidence shows that NF-kappaB activation increases the resistance to TNF-alpha -indu ced apoptosis in mesangial cells. We examined glomerular cell proliferation and apoptosis along with NF-kappaB activation in the Thy-1.1 nephritis mod el. We also evaluated TNF-alpha -induced apoptosis in cultured mesangial ce lls. Methylprednisolone treatment ameliorated mesangial hypercellularity in Thy-1.1 nephritis by decreasing proliferating cells and increasing apoptos is in the glomeruli. These effects were associated with suppressed NF-kappa B activation. This in vitro study revealed that treatment with methylpredni solone and TNF-alpha induced cultured mesangial cell apoptosis. These resul ts suggest that methylprednisolone may accelerate the resolution phase of T hy-1.1 nephritis in part by sensitizing mesangial cells to apoptosis. Copyr ight (C) 2001 S. Karger AG, Basel.