Beta 2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications
DC Field | Value | Language |
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dc.contributor.author | Noh, Hyunjin | - |
dc.contributor.author | Yu, Mi Ra | - |
dc.contributor.author | Kim, Hyun Joo | - |
dc.contributor.author | Lee, Ji Hye | - |
dc.contributor.author | Park, Byoung-Won | - |
dc.contributor.author | Wu, I-Hsien | - |
dc.contributor.author | Matsumoto, Motonobu | - |
dc.contributor.author | King, George L. | - |
dc.date.accessioned | 2021-08-11T14:44:04Z | - |
dc.date.available | 2021-08-11T14:44:04Z | - |
dc.date.issued | 2017-07 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.issn | 1523-1755 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/7423 | - |
dc.description.abstract | Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (beta 2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-a production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, beta 2AR agonists inhibited diabetes-induced tumor necrosis factor-alpha production, which was prevented by co-treatment with a selective beta 2AR blocker. To clarify the underlying mechanisms, THP-1 cells and bone marrow macrophages were exposed to high glucose. High glucose reduced beta-arrestin2, a negative regulator of NF-kappa B activation, and its interaction with I kappa B alpha. This subsequently enhanced phosphorylation of I kappa B alpha and activation of NF-kappa B. The beta 2AR agonists enhanced beta-arrestin2 and its interaction with I kappa B alpha, leading to downregulation of NF-kappa B. A siRNA specific for beta-arrestin2 reversed beta 2AR agonist-mediated inhibition of NF-kappa B activation and inflammatory cytokine production. Treatment of Zucker diabetic fatty rats with a beta 2AR agonist for 12 weeks attenuated monocyte activation as well as pro-inflammatory and pro-fibrotic responses in the kidneys and heart. Thus, beta 2AR agonists might have protective effects against diabetic renal and cardiovascular complications. | - |
dc.format.extent | 13 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Elsevier Inc. | - |
dc.title | Beta 2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1016/j.kint.2017.02.013 | - |
dc.identifier.wosid | 000403827000016 | - |
dc.identifier.bibliographicCitation | Kidney International, v.92, no.1, pp 101 - 113 | - |
dc.citation.title | Kidney International | - |
dc.citation.volume | 92 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 101 | - |
dc.citation.endPage | 113 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Urology & Nephrology | - |
dc.relation.journalWebOfScienceCategory | Urology & Nephrology | - |
dc.subject.keywordPlus | ALPHA-TOCOPHEROL SUPPLEMENTATION | - |
dc.subject.keywordPlus | PERIPHERAL-BLOOD | - |
dc.subject.keywordPlus | CYTOKINE PRODUCTION | - |
dc.subject.keywordPlus | INSULIN-RESISTANCE | - |
dc.subject.keywordPlus | MONOCYTIC CELLS | - |
dc.subject.keywordPlus | PLASMA-GLUCOSE | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | BETA | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | NEPHROPATHY | - |
dc.subject.keywordAuthor | diabetes | - |
dc.subject.keywordAuthor | fibrosis | - |
dc.subject.keywordAuthor | inflammation | - |
dc.subject.keywordAuthor | macrophages | - |
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