Glucocorticoid has long been used to treat patients with glomerulonephritis because it ameliorates mesangial cell proliferation and proteinuria, in part by suppressing nuclear factor-kappa B (NF-ĸB) activation, which regulates the transcription of various pro-inflammatory genes. Recent evidence shows that NF-ĸB activation increases the resistance to TNF-α-induced apoptosis in mesangial cells. We examined glomerular cell proliferation and apoptosis along with NF-ĸB activation in the Thy-1.1 nephritis model. We also evaluated TNF-α-induced apoptosis in cultured mesangial cells. Methylprednisolone treatment ameliorated mesangial hypercellularity in Thy-1.1 nephritis by decreasing proliferating cells and increasing apoptosis in the glomeruli. These effects were associated with suppressed NF-ĸB activation. This in vitro study revealed that treatment with methylprednisolone and TNF-α induced cultured mesangial cell apoptosis. These results suggest that methylprednisolone may accelerate the resolution phase of Thy-1.1 nephritis in part by sensitizing mesangial cells to apoptosis.

Keywords:
Apoptosis, NF-ĸB, Methylprednisolone, Glomerulonephritis, Mesangial cell
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2001
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