Back to Search
Start Over
MicroRNA-155 Silencing Enhances Inflammatory Response and Lipid Uptake in Oxidized Low-Density Lipoprotein-Stimulated Human THP-1 Macrophages
- Source :
- Journal of Investigative Medicine. 58:961-967
- Publication Year :
- 2010
- Publisher :
- SAGE Publications, 2010.
-
Abstract
- 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.
- Subjects :
- CD36
Blotting, Western
Inflammation
Biology
Transfection
General Biochemistry, Genetics and Molecular Biology
Cell Line, Tumor
medicine
Humans
Gene silencing
Gene Silencing
Scavenger receptor
Receptor
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
CD68
Macrophages
Interleukin
Lipid metabolism
General Medicine
Lipid Metabolism
Cell biology
Lipoproteins, LDL
MicroRNAs
Gene Expression Regulation
Biochemistry
Gene Knockdown Techniques
biology.protein
Cytokines
lipids (amino acids, peptides, and proteins)
medicine.symptom
Subjects
Details
- ISSN :
- 17088267 and 10815589
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Medicine
- Accession number :
- edsair.doi.dedup.....6d424964e52e14df87f4ae08f4fd8460