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Li HH, Hsu YH, Wei CC, Lee PT, Chen WC, Chang MS: Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure. Genes Immun. 2008 Jul;9(5):395-404. Epub 2008 May 22.
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. |
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