MicroRNA-149 negatively regulates TLR-triggered inflammatory response in macrophages by targeting MyD88

Guangxian Xu, Zhaobo Zhang, Yiwen Xing, Jun Wei, Zhaohui Ge, Xiaoming Liu, Ying Zhang, Xuelan Huang

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRNAs) have been shown to be important regulators of TLR signaling pathway at the post-transcriptional level. In this study, the potential role of miR-149 was explored in murine alveolar macrophage RAW264.7 cells. Our results demonstrated a dynamic change of the expressions of miR-149 expression and MyD88 in macrophage RAW264.7 upon Mycobacterium bovis Bacillus Calmette-Guerlin (BCG) infection or lipopolysaccharide (LPS) stimulation. The presence of BCG or LPS dynamically reduced the miR-149 expression, along with a substantially striking increase of MyD88 expression in these cells. More importantly, overexpression of miR-149 in RAW264.7 cells was associated with a significant decrease of MyD88 protein expression, as well as a reduced production of inflammatory mediator NF-κB 1, TNF-α and IL-6 in response to BCG infection or LPS stimulation. Further studies using immunoblotting assay against anti-MyD88 antibody and microRNA targeting luciferase reporter assay revealed that miR-149 was able to directly target the 3′-UTR of MyD88 mRNA and post-transcriptionally regulated MyD88 protein expression. These data suggested that miR-149 might be a key player of immune modulator for TLR/MyD88 signaling pathway in macrophages, which may through a mechanism of negatively regulating MyD88-dependent Toll-like receptors signaling pathway.

Original languageEnglish (US)
Pages (from-to)919-927
Number of pages9
JournalJournal of cellular biochemistry
Volume115
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • INFLAMMATORY RESPONSE
  • MyD88
  • TLR
  • microRNA-149

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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