Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides

  • Ching Hua Hsieh
  • , Cheng Shyuan Rau
  • , Jonathan Chris Jeng
  • , Yi Chun Chen
  • , Tsu Hsiang Lu
  • , Chia Jung Wu
  • , Yi Chan Wu
  • , Siou Ling Tzeng
  • , Johnson Chia Shen Yang*
  • *Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

63 Scopus citations

Abstract

Background: Lipopolysaccharide (LPS) is recognized as the most potent microbial mediator presaging the threat of invasion of Gram-negative bacteria that implicated in the pathogenesis of sepsis and septic shock. This study was designed to examine the microRNA (miRNA) expression in whole blood from mice injected with intraperitoneal LPS. Methods: C57BL/6 mice received intraperitoneal injections of varying concentrations (range, 101000 ?g) of LPS from different bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Salmonella enterica, and Serratia marcescens and were killed 2, 6, 24, and 72 h after LPS injection. Whole blood samples were obtained and tissues, including lung, brain, liver, and spleen, were harvested for miRNA expression analysis using an miRNA array (Phalanx miRNA OneArray®1.0). Upregulated expression of miRNA targets in the whole blood of C57BL/6 and Tlr4-/-mice injected with LPS was quantified using real-time RT-PCR and compared with that in the whole blood of C57BL/6 mice injected with lipoteichoic acid (LTA) from Staphylococcus aureus. Results: Following LPS injection, a significant increase of 15 miRNAs was observed in the whole blood. Among them, only 3 miRNAs showed up-regulated expression in the lung, but no miRNAs showed a high expression level in the other examined tissues. Upregulated expression of the miRNA targets (let-7d, miR-15b, miR-16, miR-25, miR-92a, miR-103, miR-107 and miR-451) following LPS injection on real-time RT-PCR was dose- and time-dependent. miRNA induction occurred after 2 h and persisted for at least 6 h. Exposure to LPS from different bacteria did not induce significantly different expression of these miRNA targets. Additionally, significantly lower expression levels of let-7d, miR-25, miR-92a, miR-103, and miR-107 were observed in whole blood of Tlr4-/- mice. In contrast, LTA exposure induced moderate expression of miR-451 but not of the other 7 miRNA targets. Conclusions: We identified a specific whole bloodderived miRNA signature in mice exposed to LPS, but not to LTA, from different gram-negative bacteria. These whole blood-derived miRNAs are promising as biomarkers for LPS exposure.

Original languageEnglish
Article number69
JournalJournal of Biomedical Science
Volume19
Issue number1
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Gram-negative bacteria
  • Gram-positive bacteria
  • Lipopolysaccharide
  • Lipoteichoic acid
  • MicroRNAs
  • Microarray
  • Toll-like receptor

Fingerprint

Dive into the research topics of 'Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides'. Together they form a unique fingerprint.

Cite this