Maruyama K, Kashihara N, Yamasaki Y, Sato M, Sugiyama H, Okamoto K, Maeshima Y, Odawara M, Sasaki J, Makino H
Department of Medicine III, Okayama University Medical School, Okayama, Japan.
Exp Nephrol. 2001;9(5):317-26. doi: 10.1159/000052627.
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-kappaB) activation, which regulates the transcription of various pro-inflammatory genes. Recent evidence shows that NF-kappaB activation increases the resistance to TNF-alpha-induced apoptosis in mesangial cells. We examined glomerular cell proliferation and apoptosis along with NF-kappaB activation in the Thy-1.1 nephritis model. We also evaluated TNF-alpha-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-kappaB activation. This in vitro study revealed that treatment with methylprednisolone and TNF-alpha 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.
