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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 1/2009

01-02-2009 | Review Article

Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease

Authors: Kengo Furuichi, Shuichi Kaneko, Takashi Wada

Published in: Clinical and Experimental Nephrology | Issue 1/2009

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Abstract

Ischemia–reperfusion injury is a main cause of acute kidney injury. Tubular necrosis and interstitial inflammatory cell infiltration are characteristic pathologic changes of acute kidney injury. The main necrotic area should be repaired with new tubular epithelial cells after the injury. On the other hand, some parts of the injured kidney progress to interstitial fibrosis, a characteristic pathologic change in chronic kidney disease. We hypothesized that interstitial infiltrating leukocytes, that are attracted and activated by chemokines, are key mediators in the pathogenesis of tubular necrosis, regeneration of the necrotic area, or interstitial fibrosis. A large number of chemokines were upregulated after ischemic injury, and chemokine receptor-expressing inflammatory cells were attracted by these chemokines. Genetic or molecular modulating experiments in the mouse model have begun to reveal the key participants and their specific roles at the levels of inflammation, regeneration, and fibrosis. Among these chemokines/chemokine receptors, our data indicated CCR2-mediated macrophage infiltration mainly affected tubular necrosis after ischemic acute kidney injury, interferon-gamma-inducible protein (IP)-10-producing macrophages participate in regeneration of tubular epithelial cells, and CX3CR1-mediated macrophages and platelet infiltration and aggregation play roles in interstitial fibrosis in chronic kidney disease. These chemokines and chemokine receptors on infiltrating inflammatory cells would be novel clinical markers or targets for therapeutic intervention.
Literature
1.
2.
Minami M, Satoh M. Chemokines and their receptors in the brain: pathophysiological roles in ischemic brain injury. Life Sci. 2003;74:321–7.CrossRefPubMed
3.
Frangogiannis NG, Entman ML. Chemokines in myocardial ischemia. Trends Cardiovasc Med. 2005;15:163–9.CrossRefPubMed
4.
Furuichi K, Wada T, Iwata Y, Sakai N, Yoshimoto K, Kobayashi Ki K, et al. Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice. Nephrol Dial Transplant. 2002;17:399–407.CrossRefPubMed
5.
Nangaku M, Inagi R, Miyata T, Fujita T. Hypoxia and hypoxia-inducible factor in renal disease. Nephron Exp Nephrol. 2008;110:e1–7.CrossRefPubMed
6.
Huang LE, Arany Z, Livingston DM, Bunn HF. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem. 1996;271:32253–9.CrossRefPubMed
7.
Salceda S, Caro J. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem. 1997;272:22642–7.CrossRefPubMed
8.
El Awad B, Kreft B, Wolber EM, Hellwig-Burgel T, Metzen E, Fandrey J, et al. Hypoxia and interleukin-1beta stimulate vascular endothelial growth factor production in human proximal tubular cells. Kidney Int. 2000;58:43–50.CrossRefPubMed
9.
Zhou J, Brune B. Cytokines and hormones in the regulation of hypoxia inducible factor-1alpha (HIF-1alpha). Cardiovasc Hematol Agents Med Chem. 2006;4:189–97.CrossRefPubMed
10.
Meldrum DR, Dinarello CA, Cleveland JC Jr, Cain BS, Shames BD, Meng X, et al. Hydrogen peroxide induces tumor necrosis factor alpha-mediated cardiac injury by a P38 mitogen-activated protein kinase-dependent mechanism. Surgery. 1998;124:291–6; discussion 297.CrossRefPubMed
11.
Nelson PJ, Ortiz BD, Pattison JM, Krensky AM. Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes. J Immunol. 1996;157:1139–48.PubMed
12.
Yasumoto K, Okamoto S, Mukaida N, Murakami S, Mai M, Matsushima K. Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kB-like binding sites of the interleukin 8 gene. J Biol Chem. 1992;267:22506–11.PubMed
13.
Lenardo MJ, Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989;58:227–9.CrossRefPubMed
14.
Cao CC, Ding XQ, Ou ZL, Liu CF, Li P, Wang L, et al. In vivo transfection of NF-kappaB decoy oligodeoxynucleotides attenuate renal ischemia/reperfusion injury in rats. Kidney Int. 2004;65:834–45.CrossRefPubMed
15.
Segerer S, Nelson PJ, Schlondorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol. 2000;11:152–76.PubMed
16.
Sato W, Kadomatsu K, Yuzawa Y, Muramatsu H, Hotta N, Matsuo S, et al. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury. J Immunol. 2001;167:3463–9.CrossRefPubMed
17.
Sato W, Takei Y, Yuzawa Y, Matsuo S, Kadomatsu K, Muramatsu T. Midkine antisense oligodeoxyribonucleotide inhibits renal damage induced by ischemic reperfusion. Kidney Int. 2005;67:1330–9.CrossRefPubMed
18.
Thurman JM, Lenderink AM, Royer PA, Coleman KE, Zhou J, Lambris JD, et al. C3a is required for the production of CXC chemokines by tubular epithelial cells after renal ischemia/reperfusion. J Immunol. 2007;178:1819–28.CrossRefPubMed
19.
Molls RR, Savransky V, Liu M, Bevans S, Mehta T, Tuder RM, et al. Keratinocyte-derived chemokine is an early biomarker of ischemic acute kidney injury. Am J Physiol Renal Physiol. 2006;290:F1187–93.CrossRefPubMed
20.
Cugini D, Azzollini N, Gagliardini E, Cassis P, Bertini R, Colotta F, et al. Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia–reperfusion. Kidney Int. 2005;67:1753–61.CrossRefPubMed
21.
Miura M, Fu X, Zhang QW, Remick DG, Fairchild RL. Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury. Am J Pathol. 2001;159:2137–45.CrossRefPubMedPubMedCentral
22.
Daemen MA, de Vries B, van’t Veer C, Wolfs TG, Buurman WA. Apoptosis and chemokine induction after renal ischemia/reperfusion. Transplantation. 2001;71:1007–11.CrossRefPubMed
23.
Popivanova BK, Koike K, Tonchev AB, Ishida Y, Kondo T, Ogawa S, et al. Accumulation of microglial cells expressing ELR motif-positive CXC chemokines and their receptor CXCR2 in monkey hippocampus after ischemia–reperfusion. Brain Res. 2003;970:195–204.CrossRefPubMed
24.
Tarzami ST, Miao W, Mani K, Lopez L, Factor SM, Berman JW, et al. Opposing effects mediated by the chemokine receptor CXCR2 on myocardial ischemia–reperfusion injury: recruitment of potentially damaging neutrophils and direct myocardial protection. Circulation. 2003;108:2387–92.CrossRefPubMed
25.
Belperio JA, Keane MP, Burdick MD, Gomperts BN, Xue YY, Hong K, et al. CXCR2/CXCR2 ligand biology during lung transplant ischemia–reperfusion injury. J Immunol. 2005;175:6931–9.CrossRefPubMed
26.
Melnikov VY, Faubel S, Siegmund B, Lucia MS, Ljubanovic D, Edelstein CL. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. J Clin Invest. 2002;110:1083–91.CrossRefPubMedPubMedCentral
27.
Day YJ, Huang L, Ye H, Linden J, Okusa MD. Renal ischemia–reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages. Am J Physiol Renal Physiol. 2005;288:F722–31.CrossRefPubMed
28.
Sung FL, Zhu TY, Au-Yeung KK, Siow YL, Karmin O. Enhanced MCP-1 expression during ischemia/reperfusion injury is mediated by oxidative stress and NF-kappaB. Kidney Int. 2002;62:1160–70.CrossRefPubMed
29.
Furuichi K, Wada T, Iwata Y, Kitagawa K, Kobayashi K, Hashimoto H, et al. Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia–reperfusion injury. J Am Soc Nephrol. 2003;14:1066–71.CrossRefPubMed
30.
Furuichi K, Wada T, Iwata Y, Kitagawa K, Kobayashi K, Hashimoto H, et al. CCR2 signaling contributes to ischemia–reperfusion injury in kidney. J Am Soc Nephrol. 2003;14:2503–15.CrossRefPubMed
31.
Rice JC, Spence JS, Yetman DL, Safirstein RL. Monocyte chemoattractant protein-1 expression correlates with monocyte infiltration in the post-ischemic kidney. Ren Fail. 2002;24:703–23.CrossRefPubMed
32.
Jo SK, Sung SA, Cho WY, Go KJ, Kim HK. Macrophages contribute to the initiation of ischaemic acute renal failure in rats. Nephrol Dial Transplant. 2006;21:1231–9.CrossRefPubMed
33.
Liu KD. Molecular mechanisms of recovery from acute renal failure. Crit Care Med. 2003;31:S572–81.CrossRefPubMed
34.
Nony PA, Schnellmann RG. Mechanisms of renal cell repair and regeneration after acute renal failure. J Pharmacol Exp Ther. 2003;304:905–12.CrossRefPubMed
35.
Bussolati B, Tetta C, Camussi G. Contribution of stem cells to kidney repair. Am J Nephrol. 2008;28:813–22.CrossRefPubMed
36.
Ghielli M, Verstrepen W, Nouwen E, De Broe ME. Regeneration processes in the kidney after acute injury: role of infiltrating cells. Exp Nephrol. 1998;6:502–7.CrossRefPubMed
37.
Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function, and association with the malignant process. Adv Cancer Res. 1997;71:241–319.CrossRefPubMed
38.
Lewington AJ, Padanilam BJ, Martin DR, Hammerman MR. Expression of CD44 in kidney after acute ischemic injury in rats. Am J Physiol Regul Integr Comp Physiol. 2000;278:R247–54.CrossRefPubMed
39.
Furuichi K, Wada T, Kitajikma S, Toyama T, Okumura T, Hara A, et al. IFN-inducible protein 10 (CXCL10) regulates tubular cell proliferation in renal ischemia–reperfusion injury. Nephron Exp Nephrol. 2008;109:c29–38.CrossRefPubMed
40.
Wada T, Sakai N, Matsushima K, Kaneko S. Fibrocytes: a new insight into kidney fibrosis. Kidney Int. 2007;72:269–73.CrossRefPubMed
41.
Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–92.CrossRefPubMed
42.
Hugo C. The thrombospondin 1-TGF-beta axis in fibrotic renal disease. Nephrol Dial Transplant. 2003;18:1241–5.CrossRefPubMed
43.
Hirschberg R, Wang S. Proteinuria and growth factors in the development of tubulointerstitial injury and scarring in kidney disease. Curr Opin Nephrol Hypertens. 2005;14:43–52.CrossRefPubMed
44.
Furuichi K, Gao JL, Murphy PM. Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia–reperfusion injury. Am J Pathol. 2006;169:372–87.CrossRefPubMedPubMedCentral
45.
Wada T, Tomosugi N, Naito T, Yokoyama H, Kobayashi K, Harada A, et al. Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis. J Exp Med. 1994;180:1135–40.CrossRefPubMed
46.
Wada T, Yokoyama H, Furuichi K, Kobayashi KI, Harada K, Naruto M, et al. Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP-1). FASEB J. 1996;10:1418–25.CrossRefPubMed
47.
Wada T, Yokoyama H, Matsushima K, Kobayashi K. Chemokines in renal diseases. Int Immunopharmacol. 2001;1:637–45.CrossRefPubMed
48.
Cascieri MA, Springer MS. The chemokine/chemokine-receptor family: potential and progress for therapeutic intervention. Curr Opin Chem Biol. 2000;4:420–7.CrossRefPubMed
49.
Proudfoot AE. Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol. 2002;2:106–15.CrossRefPubMed
50.
Grone HJ, Weber C, Weber KS, Grone EF, Rabelink T, Klier CM, et al. Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection: blocking monocyte arrest and recruitment. FASEB J. 1999;13:1371–83.CrossRefPubMed
51.
Kitagawa K, Wada T, Furuichi K, Hashimoto H, Ishiwata Y, Asano M, et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. Am J Pathol. 2004;165:237–46.CrossRefPubMedPubMedCentral
Metadata
Title
Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease
Authors
Kengo Furuichi
Shuichi Kaneko
Takashi Wada
Publication date
01-02-2009
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 1/2009
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-008-0119-5

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