MicroRNA-223 Is Upregulated in Active Tuberculosis Patients and Inhibits Apoptosis of Macrophages by Targeting FOXO3

Genet Test Mol Biomarkers. 2015 Dec;19(12):650-6. doi: 10.1089/gtmb.2015.0090. Epub 2015 Oct 27.

Abstract

Background: Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB).

Aim: In this study, we aimed to investigate the role of microRNA-223 (miR-223) in macrophage apoptosis of TB.

Methods: We analyzed apoptosis in peripheral blood macrophages of active TB patients, infected human macrophages (TDMs and MDMs) with the Mycobacterium tuberculosis (Mtb) strain H37Rv, and observed the expression of miR-223 to investigate the relationship between miR-223 and macrophage apoptosis induced by Mtb.

Results: The apoptosis rate of peripheral blood macrophages decreased in active TB patients compared with healthy controls, and miR-223 expression increased significantly in macrophages after H37Rv infection. Transfection of human macrophages (TDMs and MDMs) with miR-223 inhibited macrophage apoptosis. We also demonstrated that miR-223 directly suppressed forkhead box O3 (FOXO3), and FOXO3 played a critical role as a mediator of the biological effects of miR-223 in macrophage apoptosis. The overexpression of FOXO3 remarkably reversed the apoptosis inhibitory effect of miR-223.

Conclusion: Our data provide new clues for the essential role of miR-223 in the regulation of anti-Mtb-directed immune responses, which relies on the regulation of FOXO3 expression.

MeSH terms

  • Adult
  • Apoptosis*
  • Female
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / biosynthesis*
  • Forkhead Transcription Factors / immunology
  • Humans
  • Immunity, Innate
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / immunology
  • Middle Aged
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / metabolism*
  • Tuberculosis, Pulmonary / pathology
  • Up-Regulation*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • MIRN223 microRNA, human
  • MicroRNAs