Altered miRNAs expression profiles and modulation of immune response genes and proteins during neonatal sepsis

J Clin Immunol. 2014 Apr;34(3):340-8. doi: 10.1007/s10875-014-0004-9. Epub 2014 Feb 28.

Abstract

Purpose: The dysregulated expression of miRNAs in the immune system may be critical for immune responses to pathogens and evolve into the inflammation seen in sepsis. The aim of this study is to explore the important role of miRNAs in the regulation of the immune response during neonatal sepsis.

Methods: Using a microarray we performed the miRNA expression profiling of peripheral blood leukocytes from neonates with sepsis and uninfected neonates. Based on the predicted target genes of these miRNAs we selected 26 immune-related miRNAs out of the differentially expressed miRNAs for further testing by quantitative PCR. We simultaneously detected the immune response genes by PCR array and plasma cytokine levels using a protein chip to investigate the effect of the altered miRNAs on the immune response in neonatal sepsis.

Results: There were 10 immune regulatory miRNAs whose expression was significantly changed more than two fold in the neonates with sepsis compared with the uninfected neonates. The expression levels of 11 immune response genes and the plasma levels of 15 cytokines or receptors were significantly up- or down-regulated in the neonates with sepsis compared to the uninfected neonates. This comprehensive analysis suggests that the altered miRNAs modulate the immune response during neonatal sepsis in a way that represses the inflammatory response.

Conclusions: Our investigation demonstrated some miRNAs with altered expression levels and their probable association with the regulation of immune response during neonatal sepsis. The characteristics of the neonatal inflammatory response could be attributed to immature immune function of neonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / blood
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immunity / genetics*
  • Infant
  • Infant, Newborn
  • Male
  • MicroRNAs / genetics*
  • Models, Biological
  • RNA, Messenger / genetics
  • Risk Factors
  • Sepsis / blood
  • Sepsis / genetics*
  • Sepsis / immunology*
  • Transcriptome*

Substances

  • Cytokines
  • MicroRNAs
  • RNA, Messenger