Whole blood-derived microRNA signatures in mice exposed to lipopolysaccharides

Journal of Biomedical Science

Johnson Chia-Shen Yang²  Siou-Ling Tzeng²  Yi-Chan Wu²  Chia-Jung Wu²  Tsu-Hsiang Lu²  Yi-Chun Chen²  Jonathan Chris Jeng¹  Cheng-Shyuan Rau³  Ching-Hua Hsieh² 

[1] Business BA at University of Texas at Dallas, 800 W Campbell Road, Richardson, TX, 75080, USA;Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan;Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

关键词: Microarray;    Gram-positive bacteria;    Gram-negative bacteria;    Toll-like receptor;    Lipoteichoic acid;    Lipopolysaccharide;    MicroRNAs;   

Others  :  824707
DOI  :  10.1186/1423-0127-19-69

 received in 2012-05-25, accepted in 2012-07-16,  发布年份 2012

【 摘 要 】

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, 10–1000 μg) 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 blood–derived 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.

【 授权许可】

   
2012 Hsieh et al.; licensee BioMed Central Ltd.

【 图 表 】

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