title: Kruppel-Like Factor 2-Mediated Suppression of MicroRNA-155 Reduces the Proinflammatory Activation of Macrophages.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  KLF2-mediated suppression of miR-155 reduced the inflammatory response of macrophages.
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Shaolin
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Cardiology, XiangYang First People's Hospital Affiliated of HuBei University of Medicine, Hubei, PR China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Dazhu
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007378:Interleukins; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse