TY - JOUR
T1 - Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure
AU - Li, H. H.
AU - Hsu, Y. H.
AU - Wei, C. C.
AU - Lee, P. T.
AU - Chen, W. C.
AU - Chang, M. S.
N1 - Funding Information:
Correspondence: Professor M-S Chang, Department of Biochemistry and Molecular Biology, National Cheng Kung University, College of Medicine, Tainan 70428, Taiwan. E-mail: [email protected] This work was supported by a grant from Chi Mei Medical Center, Tainan, Taiwan. Received 24 October 2007; revised 24 January 2008; accepted 20 March 2008; published online 22 May 2008
PY - 2008/7
Y1 - 2008/7
N2 - Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl2-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-β1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1β transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-β1 and IL-1β and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.
AB - Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl2-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-β1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1β transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-β1 and IL-1β and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.
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U2 - 10.1038/gene.2008.28
DO - 10.1038/gene.2008.28
M3 - Article
C2 - 18496552
AN - SCOPUS:48349119878
SN - 1466-4879
VL - 9
SP - 395
EP - 404
JO - Genes and Immunity
JF - Genes and Immunity
IS - 5
ER -