Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure.
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 HgCl(2)-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)-beta1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 beta transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-beta1 and IL-1 beta 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.
Li
H-H
HH
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Hsu
Y-H
YH
Wei
C-C
CC
Lee
P-T
PT
Chen
W-C
WC
Chang
M-S
MS
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D007378:Interleukins; D008627:Mercuric Chloride; C422042:interleukin 20