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MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages.
MedLine Citation:
PMID:  21030878     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
Ri-sheng Huang; Guan-qiong Hu; Bin Lin; Zhi-yi Lin; Cheng-chao Sun
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Publication Detail:
Type:  Journal Article    
Journal Detail:
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:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9501229     Medline TA:  J Investig Med     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  961-7     Citation Subset:  IM    
Affiliation:
Department of Thoracic Surgery, Wenzhou Second People's Hospital, Wenzhou, China.
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