Ethyl pyruvate decreases proinflammatory gene expression in lipopolysaccharide-stimulated equine monocytes.
Abstract: Monocytes are among the initial cells that interact with circulating LPS. Binding of LPS to monocyte surface receptors triggers an intracellular signaling cascade and results in the production of proinflammatory cytokines. Ethyl pyruvate, a stable derivative of pyruvate, has been effective in mitigating LPS induced alterations in isolated human monocytes. We hypothesized that ethyl pyruvate would suppress proinflammatory gene expression in LPS-stimulated equine monocytes without affecting cell viability. Equine monocytes were isolated from whole blood using a sediment-gradient centrifugation protocol and enriched to 76% purity by adhesion to tissue culture dishes. Isolated monocytes were incubated with 0, 1, 5, 10 and 50 mM ethyl pyruvate. Cell viability, production of caspase 3/7, and caspase-3 gene expression were determined. In a separate experiment, monocytes were stimulated with LPS (0.1 ng/ml for 1h) followed by incubation with 0, 1, 5, or 10 mM ethyl pyruvate for 1 h. Proinflammatory gene expression was determined by real-time PCR. Ethyl pyruvate at 50 mM adversely affected monocyte viability. Ethyl pyruvate at 10mM or less had no significant effect on monocyte viability, and did not increase activity of caspase 3/7 nor caspase-3 gene expression. Incubation with LPS alone induced a significant upregulation in proinflammatory gene expression. Subsequent treatment of monocytes with ethyl pyruvate significantly reduced IL-8 expression in LPS stimulated monocytes at 5 mM, and IL-8, TNF-α and COX-2 at 10 mM. No beneficial effect on expression of IL-1β or IL-6 was detected. Overall, 10 mM ethyl pyruvate did not adversely affect monocyte viability and suppressed LPS-induced proinflammatory gene expression. Ethyl pyruvate may be a beneficial anti-inflammatory therapy in equine endotoxemia.
Copyright © 2011 Elsevier B.V. All rights reserved.
Publication Date: 2011-02-25 PubMed ID: 21419499DOI: 10.1016/j.vetimm.2011.02.012Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigates the effect of ethyl pyruvate on the expression of inflammatory genes in horse monocytes exposed to lipopolysaccharide (LPS). The results suggest ethyl pyruvate may send equine monocytes into a less inflammatory state without negatively impacting their viability.
Introduction
- The researchers were looking into the relationship between ethyl pyruvate, a stable derivative of pyruvate, and monocytes, which are cells that initially interact with circulating lipopolysaccharides (LPS).
- LPS bind to receptors on the surfaces of these cells, initiating a signaling cascade within the cell and the production of proinflammatory cytokines.
- Previous research has shown that ethyl pyruvate can mitigate LPS-related changes in isolated human monocytes. Hence, this research aimed to investigate whether these effects could be replicated in equine monocytes.
Methods
- Monocytes were isolated from horse blood using a specific centrifugation process, and by adhering to tissue culture dishes their purity was increased to 76%.
- These cells were then incubated with different concentrations of ethyl pyruvate, and their viability, as well as the production of caspase 3/7 (cell death-related proteins) and the expression of the caspase-3 gene, was measured.
- In a separate experiment, these monocytes were exposed to LPS and then treated with ethyl pyruvate to measure changes in the expression of proinflammatory genes.
Results
- A significant decrease in monocyte viability was observed at a high concentration of ethyl pyruvate (50mM).
- However, at concentrations of 10mM and less, ethyl pyruvate did not significantly affect monocyte viability or induce any increase in the activity of caspase 3/7 or caspase-3 gene expression.
- LPS alone significantly increased the expression of proinflammatory genes, but subsequent treatment with ethyl pyruvate reduced the expression of these genes.
- Specifically, a significant decrease was observed in IL-8 expression at 5 mM of ethyl pyruvate, and in IL-8, TNF-α, and COX-2 at 10 mM.
- However, no favourable effect on the expression of IL-1β or IL-6 was noted.
Conclusions
- The research concluded that 10 mM ethyl pyruvate did not harm monocyte viability and could suppress the expression of proinflammatory genes induced by LPS stimulation.
- Therefore, the researchers suggested that ethyl pyruvate could be useful as an anti-inflammatory treatment for equine endotoxemia.
Cite This Article
APA
Cook VL, Holcombe SJ, Gandy JC, Corl CM, Sordillo LM.
(2011).
Ethyl pyruvate decreases proinflammatory gene expression in lipopolysaccharide-stimulated equine monocytes.
Vet Immunol Immunopathol, 141(1-2), 92-99.
https://doi.org/10.1016/j.vetimm.2011.02.012 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. vcook@cvm.msu.edu
MeSH Terms
- Animals
- Caspase 3 / metabolism
- Caspase 7 / metabolism
- Cell Survival / drug effects
- Cells, Cultured
- Flow Cytometry / veterinary
- Gene Expression Regulation / drug effects
- Horses
- Inflammation / chemically induced
- Inflammation / immunology
- Inflammation / veterinary
- Lipopolysaccharides / pharmacology
- Monocytes / drug effects
- Monocytes / metabolism
- Monocytes / physiology
- Pyruvates / pharmacology
Citations
This article has been cited 5 times.- Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med 2020 Jul;34(4):1631-1641.
- Johnson LM, Holcombe SJ, Shearer TR, Watson V, Gandy J, Southwood LL, Lynch TM, Schroeder EL, Fogle CA, Sordillo LM. Multicenter Placebo-Controlled Randomized Study of Ethyl Pyruvate in Horses Following Surgical Treatment for ≥ 360° Large Colon Volvulus. Front Vet Sci 2020;7:204.
- Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
- Bloom J, Patel N, Wagmaister J, Choudhury M, Eshghi M, Konno S. Prophylactic effect of ethyl pyruvate on renal ischemia/reperfusion injury mediated through oxidative stress. Int Urol Nephrol 2019 Jan;51(1):85-92.
- Yin G, Huang J, Ma M, Suo X, Huang Z. Oyster crude polysaccharides attenuates lipopolysaccharide-induced cytokines production and PPARγ expression in weanling piglets. Springerplus 2016;5(1):677.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
