Lipopolysaccharide (LPS) induced inflammatory changes to differentially expressed miRNAs of the host inflammatory response.

ABSTRACT

In veterinary medicine, inflammation in swine is evaluated principally by clinical signs. This method is often unreliable when assessing large animal populations because of inconsistent interpretations of clinical observations. This study examined whether changes in miRNA expression can predict the severity of the inflammatory response in swine after administration of Escherichia coli lipopolysaccharide (LPS). Whole blood from swine challenged with LPS at 0.125 µg/kg to 2.0 µg/kg body weight was collected at 0, 1, 3, and 8 h post LPS-challenge. Mature miRNAs were extracted from plasma and quantitative real-time-PCR (qRT-PCR) was used to evaluate the 84 most abundant swine miRNAs found in plasma. The miRNA changes in expression were assessed using the comparative CT Method (ΔΔCT method) for normalization with an exogenous control. The results revealed that expression of ssc-let-7e-5p, ssc-mir-22-3p, and ssc-miR-146a-5p were the most significantly changed miRNA over the time course. At 1 h post-LPS, ssc-let-7e-5p decreased as the LPS dosage levels increased from 0.125 to 1.0 µg/kg. Similarly, as the LPS doses increased from 0.125 to 0.5 µg/kg, ssc-miR-22-3p levels significantly decreased at 1 h post-LPS. In the 2.0 µg/kg LPS, ssc-miR-146a-5p levels increased between 0 and 3 h post-LPS; however, expression was downregulated with a 145 % decrease from 3 to 8 h. The three miRNA biomarkers suggest potentially useful surrogate endpoints for the evaluation of inflammatory and endotoxemia responses in swine.