Journal Article

Kruppel-Like Factor 2-Mediated Suppression of MicroRNA-155 Reduces the Proinflammatory Activation of Macrophages

He, Shaolin, Li, Ming, Li, Dazhu, Yang, Liyuan

2015

Overview

Recent evidence indicates that significant interactions exist between Kruppel-like factor 2 (KLF2) and microRNAs (miRNAs) in endothelial cells. Because KLF2 is known to exert anti-inflammatory effects and inhibit the pro-inflammatory activation of monocytes, we sought to identify how inflammation-associated miR-155 is regulated by KLF2 in macrophages. Peritoneal macrophages from wild-type (WT) C57Bl/6 mice were transfected with either recombinant adenovirus vector expressing KLF2 (Ad-KLF2) or siRNA targeting KLF2 (KLF2-siRNA) for 24 h-48 h, then stimulated with oxidized low-density lipoproteins (ox-LDL, 50 μg/mL) for 24 h. Quantitative real-time polymerase chain reaction showed that KLF2 markedly reduced the expression of miR-155 in quiescent/ox-LDL-stimulated macrophages. We also found that the increased expression of miR-155, monocyte chemoattractant protein (MCP-1) and interleukin (IL)-6 and the decreased expression of the suppressor of cytokine signaling (SOCS)-1 and IL-10 in ox-LDL-treated macrophages were significantly suppressed by KLF2. Most importantly, over-expression of miR-155 could partly reverse the suppressive effects of KLF2 on the inflammatory response of macrophages. Conversely, the suppression of miR-155 in KLF2 knockdown macrophages significantly overcame the pro-inflammatory properties associated with KLF2 knockdown. Finally, Ad-KLF2 significantly attenuated the diet-induced formation of atherosclerotic lesions in apolipoprotein E-deficient (apoE(-/-)) mice, which was associated with a significantly reduced expression of miR-155 and its relative inflammatory cytokine genes in the aortic arch and in macrophages. KLF2-mediated suppression of miR-155 reduced the inflammatory response of macrophages.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Aorta / Aortic arch / Apolipoprotein E / Arteriosclerosis / Atherosclerosis / Binding sites / Bone marrow / Cardiology / Cell activation / Cells, Cultured / Chemokine CCL2 - genetics / Chemokine CCL2 - metabolism / Copper / Development and progression / Endothelial cells / Gene expression / Genetic aspects / Hospitals / Humans / Inflammation / Inflammatory response / Interleukin 10 / Interleukins - genetics / Interleukins - metabolism / Krueppel-like factor / Kruppel-Like Transcription Factors - genetics / Kruppel-Like Transcription Factors - metabolism / Lesions / Lipoproteins / Low density lipoprotein / Macrophage Activation / Macrophages / Macrophages - immunology / Macrophages - metabolism / Mice / Mice, Inbred C57BL / MicroRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Monocyte chemoattractant protein / Monocyte chemoattractant protein 1 / Monocytes / Overexpression / Oxidation / Pathogenesis / Peritoneum / Physiological aspects / Plaque, Atherosclerotic - metabolism / Polymerase chain reaction / Prevention / Proteins / Ribonucleic acid / RNA / siRNA