MicroRNA-155 silencing enhances inflammatory response and lipid uptake in oxidized low-density lipoprotein-stimulated human THP-1 macrophages.

  • Huang R
  • Hu G
  • Lin B
 et al. 
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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.

Author-supplied keywords

  • Blotting
  • Cell Line
  • Chromatography
  • Cytokines
  • Cytokines: metabolism
  • Dose-Response Relationship
  • Drug
  • Gene Expression Regulation
  • Gene Expression Regulation: drug effects
  • Gene Knockdown Techniques
  • Gene Silencing
  • Gene Silencing: drug effects
  • High Pressure Liquid
  • Humans
  • Inflammation
  • Inflammation: chemically induced
  • Inflammation: genetics
  • Inflammation: metabolism
  • LDL
  • LDL: pharmacology
  • Lipid Metabolism
  • Lipid Metabolism: drug effects
  • Lipoproteins
  • Macrophages
  • Macrophages: drug effects
  • Macrophages: metabolism
  • MicroRNAs
  • MicroRNAs: genetics
  • Transfection
  • Tumor
  • Western

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Authors

  • Ri-sheng Huang

  • Guan-qiong Hu

  • Bin Lin

  • Zhi-yi Lin

  • Cheng-chao Sun

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