| MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages. | |
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MedLine Citation:
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PMID: 21030878 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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It has been proposed that the inflammatory response of monocytes/macrophages induced by oxidized low-density lipoprotein (oxLDL) is a key event in the pathogenesis of atherosclerosis. MicroRNA-155 (miR-155) is an important regulator of the immune system and has been shown to be involved in acute inflammatory response. However, the function of miR-155 in oxLDL-stimulated inflammation and atherosclerosis remains unclear. Here, we show that the exposure of human THP-1 macrophages to oxLDL led to a marked up-regulation of miR-155 in a dose-dependent manner. Silencing of endogenous miR-155 in THP-1 cells using locked nucleic acid-modified antisense oligonucleotides significantly enhanced oxLDL-induced lipid uptake, up-regulated the expression of scavenger receptors (lectinlike oxidized LDL receptor-1, cluster of differentiation 36 [CD36], and CD68), and promoted the release of several cytokines including interleukin (IL)-6, -8, and tumor necrosis factor α (TNF-α). Luciferase reporter assay showed that targeting miR-155 promoted nuclear factor-kappa B (NF-κB) nuclear translocation and potentiated the NF-κB-driven transcription activity. Moreover, miR-155 knockdown resulted in a marked increase in the protein amount of myeloid differentiation primary response gene 88 (MyD88), an important adapter protein used by Toll-like receptors to activate the NF-κB pathway. Our data demonstrate that miR-155 serves as a negative feedback regulator in oxLDL-stimulated THP-1 inflammatory responses and lipid uptake and thus might have potential therapeutic implications in atherosclerosis. |
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Authors:
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Ri-sheng Huang; Guan-qiong Hu; Bin Lin; Zhi-yi Lin; Cheng-chao Sun |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of investigative medicine : the official publication of the American Federation for Clinical Research Volume: 58 ISSN: 1708-8267 ISO Abbreviation: J. Investig. Med. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9501229 Medline TA: J Investig Med Country: Canada |
Other Details:
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Languages: eng Pagination: 961-7 Citation Subset: IM |
Affiliation:
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Department of Thoracic Surgery, Wenzhou Second People's Hospital, Wenzhou, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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