Amelioration of Renal Ischemia-Reperfusion Injury by Inhibition of IL-6 Production in the Poloxamer 407-Induced Mouse Model of Hyperlipidemia
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- Sharyo Satoru
- Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Japan Medicinal Safety Research Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., Japan
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- Kumagai Kazuyoshi
- Medicinal Safety Research Laboratories, R&D Division, Daiichi-Sankyo Co., Ltd., Japan
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- Yokota-Ikeda Naoko
- Nephrology Division, Miyazaki Prefectural Miyazaki Hospital, Japan
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- Ito Katsuaki
- Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Japan
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- Ikeda Masahiro
- Department of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Japan
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説明
It is largely unknown whether hyperlipidemia is involved in the pathobiology of renal ischemia–reperfusion (I/R) injury that is an important cause of acute kidney injury. Here we studied the effect of experimental dyslipidemia on renal I/R injury. Renal I/R injury was less severe in hyperlipidemic mice treated with poloxamer 407 than in the control mice. Cytokine analyses revealed decreased levels of renal and serum IL-6 in the hyperlipidemic mice after renal I/R. Protection from renal I/R injury in the hyperlipidemic mice was diminished by administration of recombinant IL-6. Concanavalin A–induced IL-6 release from cultured splenocytes derived from the hyperlipidemic mice was lower than that from splenocytes of normal mice. In hypercholesterolemic apolipoprotein E–knockout mice, in which renal I/R injury is less severe than in control mice, renal I/R–induced IL-6 production was also less than that in controls. In angiopoietin-like 3–deficient mice, which were hypolipidemic, renal dysfunction and renal IL-6 level after I/R were similar to those of control mice. Our data indicate that the presence of experimental hyperlipidemia may be associated with a decreased risk of renal I/R injury, possibly mediated by reduced renal IL-6 production after the insult and extend the notion that an anti-IL6 agent would be useful for the treatment of acute kidney injury.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 110 (1), 47-54, 2009
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205179790464
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- NII論文ID
- 10025736569
- 130000106869
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10225684
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- PubMed
- 19403996
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- 本文言語コード
- en
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