Glucocorticoids inhibit lipopolysaccharide-mediated inflammatory response by downregulating microRNA-155: a novel anti-inflammation mechanism

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• 作者：Yijie Zheng^a ; ^b ; ¹ ; Shudao Xiong^a ; ^c ; ¹ ; Pei Jiang^a ; ^b ; Ronghua Liu^a ; Xiaoming Liu^a ; Jing Qian^a ; Xiujuan Zheng^a ; ^b ; Yiwei Chu^a ; ^b ; ^{yiwei_chu@126.com}
• 关键词：Lipopolysaccharide ; miRNAs ; Corticosteroids ; RAW264.7 ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 April, 2012
• 卷：52
• 期：8
• 页码：1307-1317
• 文件大小：1405 K

摘要

Glucocorticoids (GCs) are among the most widely used and effective therapies for many chronic inflammatory diseases. Although attempts have been made to identify important protein-coding genes and pathways involved in the anti-inflammatory effect of GCs, knowledge of genomic aberrations associated with noncoding genes, such as micro-RNAs (miRNAs), and their contributions is relatively limited. In this study, a systematic screening of the miRNA expression profile by microarray showed that GCs inhibited the expression of miR-155 in lipopolysaccharide (LPS)-induced macrophage inflammatory responses. Overexpression of miR-155 markedly reversed the suppressive action of GCs, whereas inhibition of miR-155 exhibited an effect similar to that of GCs on LPS-treated RAW264.7 cells, indicating miR-155 to be a functional regulator in the anti-inflammatory effect of GCs. Furthermore, GCs inhibited miR-155 expression in a GC receptor- and NF-魏B-dependent manner. Bioinformatics analysis and luciferase assay revealed that the NF-魏B binding site located in the promoter region of the B-cell integration cluster was important in mediating the GC-driven suppression of miR-155 in response to LPS stimulation. In addition, the combination of treatment with GCs and inhibition of miR-155 enhanced the anti-inflammatory effect of GCs on LPS-stimulated RAW264.7 cells. Therefore, we identify miR-155 to be a novel target through which GCs exert their anti-inflammatory effect on the LPS-induced macrophage inflammatory response. These findings may provide a basic rationale for new approaches in the effort to develop anti-inflammatory therapeutics.