Kruppel-Like Factor 2-Mediated Suppression of MicroRNA-155 Reduces the Proinflammatory Activation of MacrophagesReport as inadecuate




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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.

Approach and 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.

Conclusion

KLF2-mediated suppression of miR-155 reduced the inflammatory response of macrophages.



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

Source: http://plos.srce.hr/



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