Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation.
Abstract: In horses, insights into the innate immune processes in acute systemic inflammation are limited even though these processes may be highly important for future diagnostic and therapeutic advances in high-mortality disease conditions as the systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, the aim of this study was to investigate the expression of 31 selected blood leukocyte immune genes in an equine model of acute systemic inflammation to identify significantly regulated genes and to describe their expression dynamics during a 24-h experimental period. Systemic inflammation was induced in 6 adult horses by the intravenous injection of 1 μg lipopolysaccharide (LPS) per kg btw. Sixteen blood samples were collected for each horse at predetermined intervals and analyzed by reverse transcription quantitative real-time PCR. Post-induction expression levels for each gene were compared with baseline levels. Results: Systemic inflammation was confirmed by the presence of clinical and hematological changes which were consistent with SIRS. The clinical response to LPS was transient and brief as all horses except one showed unaltered general demeanor after 24 h. Twenty-two leukocyte genes were significantly regulated at at least one time point during the experimental period. By close inspection of the temporal responses the dynamic changes in mRNA abundance revealed a very rapid onset of both pro- and anti-inflammatory mediators and a substantial variation in both expression magnitudes and duration of changes between genes. A majority of the 22 significantly regulated genes peaked within the first 8 h after induction, and an on-going, albeit tightly controlled, regulation was seen after 24 h despite approximate clinical recovery. Conclusions: This first broad study of gene expressions in blood leukocytes during equine acute LPS-induced systemic inflammation thoroughly characterized a highly regulated and dynamic innate immune response. These results provide new insights into the molecular mechanisms of equine systemic inflammation.
Publication Date: 2015-06-16 PubMed ID: 26076814PubMed Central: PMC4467047DOI: 10.1186/s12917-015-0450-5Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on studying the expression of selected immune genes in horses during acute systemic inflammation. The study was conducted to provide insights into innate immune processes which can be important for diagnostics and treatment advancements in diseases like systemic inflammatory response syndrome (SIRS) and sepsis.
Objective of the Study
- The main aim of the study was to explore the reaction of 31 selected leukocyte immune genes in an equine model of acute systemic inflammation, identify significantly regulated genes and understand their expression dynamics over a 24-hour experimental period.
Study Methodology
- Systemic inflammation was induced in six adult horses via intravenous injection of 1 μg lipopolysaccharide (LPS) per kg body weight.
- For each horse, sixteen blood samples were collected at predetermined time intervals and analysed using reverse transcription quantitative real-time PCR.
- The post-induction expression levels of each gene were compared with baseline levels.
Results of the Study
- The induction of systemic inflammation was confirmed with the presence of SIRS consistent clinical and hematological changes.
- LPS-induced clinical response was transient and short-lived as all but one horse showed unchanged general demeanor after 24 hours.
- Twenty-two out of thirty-one leukocyte genes displayed significant regulation at least at one time point during the experiment.
- Detailed observation of temporal responses revealed swift onset of both pro- and anti-inflammatory mediators and a substantial variation in expression magnitudes and duration of changes across genes.
- Most of the 22 significantly regulated genes peaked within the first 8 hours post-induction. Additionally, despite clinical recovery around the 24-hour mark, ongoing and tightly regulated control was still observed.
Conclusion
- This first expansive study of gene expressions in blood leukocytes during equine acute LPS-induced systemic inflammation characterized a highly regulated and dynamic innate immune response.
- These results brought forth new insights into the molecular mechanisms of equine systemic inflammation and can have important implications for future diagnostic and therapeutic methods for high-mortality diseases such as SIRS and sepsis.
Cite This Article
APA
Vinther AM, Skovgaard K, Heegaard PM, Andersen PH.
(2015).
Dynamic expression of leukocyte innate immune genes in whole blood from horses with lipopolysaccharide-induced acute systemic inflammation.
BMC Vet Res, 11, 134.
https://doi.org/10.1186/s12917-015-0450-5 Publication
Researcher Affiliations
- Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark. amhl@sund.ku.dk.
- Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark. kesk@vet.dtu.dk.
- Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark. pmhh@vet.dtu.dk.
- Department of Clinical Sciences, Faculty of Veterinary and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden. pia.haubro.andersen@slu.se.
MeSH Terms
- Animals
- Cross-Over Studies
- Female
- Gene Expression Regulation / drug effects
- Horse Diseases / blood
- Horse Diseases / chemically induced
- Horse Diseases / metabolism
- Horses
- Immunity, Innate / drug effects
- Immunity, Innate / physiology
- Inflammation / chemically induced
- Inflammation / metabolism
- Inflammation / veterinary
- Leukocytes / drug effects
- Leukocytes / metabolism
- Lipopolysaccharides / toxicity
- Male
- Transcriptome
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Citations
This article has been cited 8 times.- Mukhopadhyay A, Cook SR, SanMiguel P, Ekenstedt KJ, Taylor SD. TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion.. Sci Rep 2023 Jan 27;13(1):1486.
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