| Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 20693423 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Overwhelming evidence suggests that ischemia-reperfusion injury of the kidney is an inflammatory disease mediated by innate and adoptive immune systems. The neuronal guidance molecule netrin-1 was shown to modulate inflammatory responses. Given that ischemic kidney is particularly prone to reperfusion-elicited inflammation, we sought to determine the function of netrin-1 and its receptor UNC5B in ischemia-reperfusion-induced inflammation. Renal ischemia-reperfusion caused a rapid decrease in serum netrin-1 levels. Administration of recombinant netrin-1 before or after renal ischemia-reperfusion reduced kidney injury, apoptosis, monocyte and neutrophil infiltration, and cytokine (IL-6, IL-1beta, and TNF-alpha) and chemokine (MCP-1, macrophage-derived cytokine, monokine-induced IFN-gamma, keratinocyte-derived chemokine, and chemokine with 6 cysteines) production. Analysis for different netrin-1 receptors on leukocytes showed very high expression of UNC5B but not UNC5C, UNC5D, neogenin, or deleted in colorectal cancer. Expression of UNC5A was low. Neutralization of UNC5B receptor reduced netrin-1-mediated protection against renal ischemia-reperfusion injury, and it increased monocyte and neutrophil infiltration, as well as serum and renal cytokine and chemokine production, with increased kidney injury and renal tubular cell apoptosis. Finally, investigation into netrin-1's effect on CD4 T cell stimulation showed suppression of Th1/Th2/Th17 cytokine (IL-2, IL-6, IL-10, IL-13, IL-17, IFN-gamma, IL-4, and TNF-alpha) production in vitro. Our studies demonstrate that netrin-1 acting through UNC5B receptor reduces renal ischemia-reperfusion injury and its associated renal inflammation. |
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Authors:
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Raghu Kempegowda Tadagavadi; Weiwei Wang; Ganesan Ramesh |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-06 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-03 Completed Date: 2010-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3750-8 Citation Subset: AIM; IM |
Affiliation:
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Division of Nephrology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Disease Models, Animal Inflammation Mediators / physiology* Interleukin-17 / biosynthesis* Kidney Diseases / immunology, pathology, physiopathology, prevention & control* Kidney Function Tests Male Mice Mice, Inbred C57BL Nerve Growth Factors / physiology* Receptors, Cell Surface / antagonists & inhibitors, physiology* Reperfusion Injury / immunology, pathology, physiopathology, prevention & control* Th1 Cells / immunology*, metabolism, pathology Th2 Cells / immunology*, metabolism, pathology Tumor Suppressor Proteins / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Inflammation Mediators; 0/Interleukin-17; 0/Nerve Growth Factors; 0/Receptors, Cell Surface; 0/Tumor Suppressor Proteins; 0/netrin receptors; 158651-98-0/netrin-1 |
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