Abstract
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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References
Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB . Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 2004; 22: 929–979.
Hsing CH, Ho CL, Chang LY, Lee YL, Chuang SS, Chang MS . Tissue microarray analysis of interleukin-20 expression. Cytokine 2006; 35: 44–52.
Parrish-Novak J, Xu W, Brender T, Yao L, Jones C, West J et al. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem 2002; 277: 47517–47523.
Hsieh MY, Chen WY, Jiang MJ, Cheng BC, Huang TY, Chang MS . Interleukin-20 promotes angiogenesis in a direct and indirect manner. Genes Immun 2006; 7: 234–242.
Chen WY, Cheng BC, Jiang MJ, Hsieh MY, Chang MS . IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2006; 26: 2090–2095.
Hsu YH, Li HH, Hsieh MY, Liu MF, Huang KY, Chin LS et al. Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis. Arthritis Rheum 2006; 54: 2722–2733.
Wei CC, Chen WY, Wang YC, Chen PJ, Lee JY, Wong TW et al. Detection of IL-20 and its receptors on psoriatic skin. Clin Immunol 2005; 117: 65–72.
Rana A, Sathyanarayana P, Lieberthal W . Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications. Apoptosis 2001; 6: 83–102.
Lieberthal W, Koh JS, Levine JS . Necrosis and apoptosis in acute renal failure. Semin Nephrol 1998; 18: 505–518.
Devarajan P . Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 2006; 17: 1503–1520.
Yamada T . [Studies on the mechanisms of renal damages induced by nephrotoxic compounds]. Nihon Hoigaku Zasshi 1995; 49: 447–457.
Liu XY, Jin TY, Nordberg GF . Increased urinary calcium and magnesium excretion in rats injected with mercuric chloride. Pharmacol Toxicol 1991; 68: 254–259.
Chaudhari A, Kirschenbaum MA . Alterations in rabbit renal microvascular prostanoid synthesis in acute renal failure. Am J Physiol 1988; 254: F684–F688.
Ho AS, Moore KW . Interleukin-10 and its receptor. Ther Immunol 1994; 1: 173–185.
Deng J, Kohda Y, Chiao H, Wang Y, Hu X, Hewitt SM et al. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 2001; 60: 2118–2128.
Okusa MD . The inflammatory cascade in acute ischemic renal failure. Nephron 2002; 90: 133–138.
Lazzeri M . The physiological function of the urothelium—more than a simple barrier. Urol Int 2006; 76: 289–295.
Ghielli M, Verstrepen W, Nouwen E, De Broe ME . Regeneration processes in the kidney after acute injury: role of infiltrating cells. Exp Nephrol 1998; 6: 502–507.
Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 2001; 104: 9–19.
Hsing CH, Chiu CJ, Chang LY, Hsu CC, Chang MS . IL-19 in involved in the pathogenesis of endotoxic shock. Shock 2008; 29: 7–15.
Sauane M, Gopalkrishnan RV, Sarkar D, Su ZZ, Lebedeva IV, Dent P et al. MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev 2003; 14: 35–51.
Aggarwal S, Takada Y, Mhashilkar AM, Sieger K, Chada S, Aggarwal BB . Melanoma differentiation-associated gene-7/IL-24 gene enhances NF-kappa B activation and suppresses apoptosis induced by TNF. J Immunol 2004; 173: 4368–4376.
Khan S, Cleveland RP, Koch CJ, Schelling JR . Hypoxia induces renal tubular epithelial cell apoptosis in chronic renal disease. Lab Invest 1999; 79: 1089–1099.
Hauser P, Oberbauer R . Tubular apoptosis in the pathophysiology of renal disease. Wien Klin Wochenschr 2002; 114: 671–677.
Miyazawa K, Suzuki K, Ikeda R, Moriyama MT, Ueda Y, Katsuda S . Apoptosis and its related genes in renal epithelial cells of the stone-forming rat. Urol Res 2005; 33: 31–38.
Edelstein CL . What is the role of tubular epithelial cell apoptosis in polycystic kidney disease (PKD)? Cell Cycle 2005; 4: 1550–1554.
Kim YK, Kim HJ, Kwon CH, Kim JH, Woo JS, Jung JS et al. Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells. J Appl Toxicol 2005; 25: 374–382.
Zhuang S, Yan Y, Daubert RA, Han J, Schnellmann RG . ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells. Am J Physiol 2007; 292: F440–F447.
Kunduzova OR, Bianchi P, Pizzinat N, Escourrou G, Seguelas MH, Parini A et al. Regulation of JNK/ERK activation, cell apoptosis, and tissue regeneration by monoamine oxidases after renal ischemia-reperfusion. FASEB J 2002; 16: 1129–1131.
Hay ED, Zuk A . Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995; 26: 678–690.
Dai C, Yang J, Liu Y . Transforming growth factor-beta1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling. J Biol Chem 2003; 278: 12537–12545.
Basile DP, Rovak JM, Martin DR, Hammerman MR . Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury. Am J Physiol 1996; 270: F500–F509.
Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke T, Somerset H et al. Cisplatin-induced ARF is associated with an increase in the cytokines IL-1{beta},IL-18, IL-6 and neutrophil infiltration in the kidney. J Pharmacol Exp Ther 2007; 322: 8–15.
Otkjaer K, Kragballe K, Johansen C, Funding AT, Just H, Jensen UB et al. IL-20 gene expression is induced by IL-1beta through mitogen-activated protein kinase and NF-kappaB-dependent mechanisms. J Invest Dermatol 2007; 127: 1326–1336.
Girardi G, Elias MM . Evidence for renal ischaemia as a cause of mercuric chloride nephrotoxicity. Arch Toxicol 1995; 69: 603–607.
Brezis M, Epstein FH . Cellular mechanisms of acute ischemic injury in the kidney. Annu Rev Med 1993; 44: 27–37.
Wei CC, Hsu YH, Li HH, Wang YC, Hsieh MY, Chen WY et al. IL-20: biological functions and clinical implications. J Biomed Sci 2006; 13: 601–612.
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This work was supported by a grant from Chi Mei Medical Center, Tainan, Taiwan.
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Li, HH., Hsu, YH., Wei, CC. et al. Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure. Genes Immun 9, 395–404 (2008). https://doi.org/10.1038/gene.2008.28
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DOI: https://doi.org/10.1038/gene.2008.28
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