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 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.
Maruyama
K
K
Department of Medicine III, Okayama University Medical School, Okayama, Japan.
Kashihara
N
N
Yamasaki
Y
Y
Sato
M
M
Sugiyama
H
H
Okamoto
K
K
Maeshima
Y
Y
Odawara
M
M
Sasaki
J
J
Makino
H
H
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology*; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005938:Glucocorticoids; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone