Adora2b Adenosine Receptor Signaling Protects during Acute Kidney Injury via Inhibition of Neutrophil-Dependent TNF-alpha Release
DC Field | Value | Language |
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dc.contributor.author | Grenz, Almut | - |
dc.contributor.author | Kim, Jae-Hwan | - |
dc.contributor.author | Bauerle, Jessica D. | - |
dc.contributor.author | Tak, Eunyoung | - |
dc.contributor.author | Eltzschig, Holger K. | - |
dc.contributor.author | Clambey, Eric T. | - |
dc.date.accessioned | 2021-09-06T13:31:29Z | - |
dc.date.available | 2021-09-06T13:31:29Z | - |
dc.date.created | 2021-06-15 | - |
dc.date.issued | 2012-11-01 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/106960 | - |
dc.description.abstract | Renal ischemia is among the leading causes of acute kidney injury (AKI). Previous studies have shown that extracellular adenosine is a prominent tissue-protective cue elicited during ischemia, including signaling events through the adenosine receptor 2b (Adora2b). To investigate the functional role of Adora2b signaling in cytokine-mediated inflammatory pathways, we screened wild-type and Adora2b-deficient mice undergoing renal ischemia for expression of a range of inflammatory cytokines. These studies demonstrated a selective and robust increase of TNF-alpha levels in Adora2b-deficient mice following renal ischemia and reperfusion. Based on these findings, we next sought to understand the contribution of TNF-alpha on ischemic AKI through a combination of loss- and gain-of-function studies. Loss of TNF-alpha, through either Ab blockade or study of Tnf-alpha-deficient animals, resulted in significantly attenuated tissue injury and improved kidney function following renal ischemia. Conversely, transgenic mice with overexpression of TNF-alpha had significantly pronounced susceptibility to AKI. Furthermore, neutrophil depletion or reconstitution of Adora2b(-/-) mice with Tnf-alpha-deficient neutrophils rescued their phenotype. In total, these data demonstrate a critical role of adenosine signaling in constraining neutrophil-dependent production of TNF-alpha and implicate therapies targeting TNF-alpha in the treatment of ischemic AKI. The Journal of Immunology, 2012, 189: 4566-4573. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.subject | ISCHEMIA-REPERFUSION INJURY | - |
dc.subject | MEDIATED TISSUE PROTECTION | - |
dc.subject | ACUTE-RENAL-FAILURE | - |
dc.subject | KNOCKOUT MICE | - |
dc.subject | CARDIAC-SURGERY | - |
dc.subject | T-CELLS | - |
dc.subject | DISEASE | - |
dc.subject | INFLAMMATION | - |
dc.subject | MECHANISMS | - |
dc.subject | HYPOXIA | - |
dc.title | Adora2b Adenosine Receptor Signaling Protects during Acute Kidney Injury via Inhibition of Neutrophil-Dependent TNF-alpha Release | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Jae-Hwan | - |
dc.identifier.doi | 10.4049/jimmunol.1201651 | - |
dc.identifier.wosid | 000310200600044 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.189, no.9, pp.4566 - 4573 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 189 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 4566 | - |
dc.citation.endPage | 4573 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | ISCHEMIA-REPERFUSION INJURY | - |
dc.subject.keywordPlus | MEDIATED TISSUE PROTECTION | - |
dc.subject.keywordPlus | ACUTE-RENAL-FAILURE | - |
dc.subject.keywordPlus | KNOCKOUT MICE | - |
dc.subject.keywordPlus | CARDIAC-SURGERY | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | HYPOXIA | - |
dc.subject.keywordAuthor | ISCHEMIA-REPERFUSION INJURY | - |
dc.subject.keywordAuthor | ACUTE-RENAL-FAILURE | - |
dc.subject.keywordAuthor | MEDIATED TISSUE PROTECTION | - |
dc.subject.keywordAuthor | MARROW-DERIVED CELLS | - |
dc.subject.keywordAuthor | KNOCKOUT MICE | - |
dc.subject.keywordAuthor | ISCHEMIA/REPERFUSION INJURY | - |
dc.subject.keywordAuthor | CISPLATIN NEPHROTOXICITY | - |
dc.subject.keywordAuthor | IMMUNE-RESPONSE | - |
dc.subject.keywordAuthor | CARDIAC-SURGERY | - |
dc.subject.keywordAuthor | T-CELLS | - |
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