Role of interleukin-10 in rat mesangioproliferative glomerulonephritis.
Interleukin-10 (IL-10) has been recognized as a growth factor for rat mesangial cells in vitro; however, its role in mesangioproliferative glomerulonephritis is unknown. We studied the expression of IL-10 mRNA in the rat anti-Thy-1 model of mesangioproliferative glomerulonephritis (experiment 1) and, subsequently, the effects of blocking IL-10 during anti-Thy-1 nephritis using the IL-10 inhibitor, AS101 (experiment 2). In experiment 1, PCR analysis failed to detect IL-10 mRNA in normal rat kidney, however, a clear signal for IL-10 mRNA was evident on day 6 of anti-Thy-1 nephritis. In situ hybridization showed IL-10 mRNA expression in focal glomerular areas in anti-Thy-1 nephritis. Combined in situ hybridization and immunohistochemistry showed that glomerular IL-10 mRNA was expressed by both macrophages and mesangial cells. In experiment 2, treatment with AS101 significantly downregulated renal IL-10 gene expression, as demonstrated by semiquantitative PCR. However, the induction of glomerular hypercellularity, mesangial proliferation (PCNA+ cells), mesangial cell activation (alpha-SMA expression) and macrophage accumulation (ED1+ cells) seen in saline-treated anti-Thy-1 nephritis was unaffected by AS101 treatment. In conclusion, renal IL-10 gene expression is upregulated during pathological mesangial cell proliferation in rats with anti-Thy-1 nephritis. However, the inability of IL-10 suppression with AS101 to prevent anti-Thy-1 disease suggests that IL-10 is not essential for pathological mesangial cell proliferation.
Robertson
Tara E
TE
Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Nikolic-Paterson
David J
DJ
Tesch
Greg H
GH
Foti
Rita A
RA
Atkins
Robert C
RC
Chadban
Steven J
SJ
D000818:Animals; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D012333:RNA, Messenger; D016753:Interleukin-10