Suppression of glomerulosclerosis by adenovirus-mediated IL-10 expression in the kidney.
Glomerulosclerosis is a common morphologic result seen in almost all progressed renal diseases, and is the characteristic change in focal segmental glomerulosclerosis (FSGS). The most convincing hypothesis for glomerulosclerosis is cytokine-mediated injury by infiltrating immune cells in the glomerulus and tubulointerstitial area. This study investigated whether the anti-inflammatory effect of interleukin-10 (IL-10) when expressed by a recombinant adenoviral vector can prevent the onset of glomerulosclerosis in FGS/Kist mice (an animal model with naturally occurring renal failure initiated by FSGS). Each group of mice received recombinant adenoviruses encoding human IL-10 (Ad:hIL-10) by intraparenchymal injection at 6 weeks and were examined for cytokine expression, glomerular sclerotic index, and proteinuria. After injection of Ad:hIL-10 to the kidney, IL-10 expression was found to last over 20 days. Mice treated with Ad:hIL-10 were shown to have a significant reduction in the glomerular sclerotic index at 10 weeks when compared to control groups. The level of proteinuria in Ad:hIL-10-treated mice was also significantly reduced. About 50% of the urine samples of naive and Ad:LacZ-treated groups had severe levels of proteinuria. By contrast, at 10 weeks the group treated with Ad:hIL-10 had lower levels of proteinuria and transforming growth factor-beta1 (TGF-beta1) expression. These results demonstrate that IL-10 effectively prevents the development of glomerulosclerosis in FGS/Kist mice, and IL-10 gene therapy may be of use for the treatment of renal failure.
Choi
Y-K
YK
Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu, Republic of Korea.
Kim
Y-J
YJ
Park
H-S
HS
Choi
K
K
Paik
S-G
SG
Lee
Y-I
YI
Park
J-G
JG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000628:therapy*; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics*; D007668:Kidney / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods*; D001616:beta-Galactosidase / Q000235:genetics
D016753:Interleukin-10; D001616:beta-Galactosidase