title: Methylprednisolone accelerates the resolution of glomerulonephritis by sensitizing mesangial cells to apoptosis.
abstract: 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.
authors.affiliation: Department of Medicine III, Okayama University Medical School, Okayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: N
authors.initials: N
authors.lastname: Kashihara
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Sugiyama
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Maeshima
authors.forename: M
authors.initials: M
authors.lastname: Odawara
authors.forename: J
authors.initials: J
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone