Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencing.
Authors: Parkinson Nicholas J, Buechner-Maxwell Virginia A, Witonsky Sharon G, Pleasant R Scott, Werre Stephen R, Ahmed S Ansar
Journal: PloS one
Summary
# Editorial Summary: MicroRNA responses to endotoxaemia in equine immune cells Lipopolysaccharide (LPS) endotoxaemia drives severe systemic inflammation in horses much like in humans, yet the regulatory mechanisms governing this response remain poorly characterised at the molecular level. Parkinson and colleagues used next-generation sequencing to map microRNA expression in equine peripheral blood mononuclear cells at baseline and following four-hour LPS stimulation, validating key findings through quantitative PCR. Only miR-155 showed significant upregulation in response to LPS, with expression changes tracking closely alongside tumour necrosis factor-α production, whilst eight other microRNAs (notably miR-146a and miR-146b) demonstrated time-dependent expression shifts independent of endotoxin exposure. Bioinformatic analysis revealed that miR-155 likely targets critical immune regulators including SOCS1, TAB2 and phosphoinositide-3-kinase pathway elements, positioning it as a key modulator of the acute inflammatory cascade. The substantial genetic conservation of miR-155 and its promoter between horses and humans, combined with remarkably similar baseline and LPS-stimulated expression patterns, validates the horse as a powerful comparative model for understanding microRNA-mediated immune dysregulation during sepsis—findings with potential implications for managing endotoxaemia-related conditions such as colitis and laminitis.
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Practical Takeaways
- •Horses share similar microRNA-mediated inflammatory responses to endotoxin as humans, making them valuable models for understanding sepsis pathophysiology and potentially developing comparative therapeutic strategies
- •MiR-155 appears to be a key regulatory checkpoint in equine endotoxemic inflammation and could be a future diagnostic or therapeutic target for managing gram-negative sepsis in horses
- •This foundational characterization of equine immune microRNA expression provides a reference resource for understanding inflammatory cascade mechanisms in equine sepsis and endotoxemia
Key Findings
- •miR-155 was the only microRNA significantly upregulated by LPS in equine peripheral blood mononuclear cells, with expression changes paralleling TNF-α concentration
- •miR-155 precursor gene and promoter regions show extensive conservation between horses and humans, suggesting similar inflammatory mechanisms
- •Target predictions indicate miR-155 influences acute inflammatory response through SOCS1, TAB2, and PI3K signaling pathway regulation
- •Basal and LPS-stimulated microRNA expression patterns in equine leukocytes are similar to those described in human leukocytes