Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils.
Abstract: Glucocorticoids have potent anti-inflammatory properties and are frequently used for the treatment of domestic animal species, including horses. They induce a down-regulation of multiple inflammatory pathways through both genomic and non-genomic effects. Currently, little is known on the effects of glucocorticoids on equine peripheral blood neutrophils. Objective: Dexamethasone (DEX), a potent synthetic glucocorticoid, inhibits the functions of equine peripheral blood neutrophils through both genomic and non-genomic effects. Methods: Six healthy adult mixed breed female horses. Methods: To assess the genomic effects of DEX, peripheral blood neutrophils were isolated using a gradient technique and incubated 6 h with 100 ng/ml LPS and 10(-6) M DEX alone, or combined with the glucocorticoid receptor (GR) inhibitor RU486 (10(-5) M). Messenger RNA for IL-8, TNF-alpha and TLR-4 were measured using real-time RT-PCR. The non-genomic effects of DEX were studied in neutrophils incubated with 5 microM dichlorodihydrofluorescein (DCF) and 10(-6) M DEX 5, 10 and 15 min prior to being stimulated with 5 ng/ml phorbol myristate acetate. Neutrophils were similarly co-incubated with DEX (10(-6) M, 15 min) and RU486 (10(-5) M) to evaluate the contribution of the GR to these effects. The oxidation of DCF was studied using flow-cytometry. Results: Neutrophils stimulation with LPS resulted in a significant increase in IL-8, TNF-alpha and TLR-4 mRNA expressions (p<0.0001); incubation with DEX significantly down-regulated this process (p<0.0001). DEX significantly reduced oxidation of DCF after 10 and 15 min of incubation (p<0.0001). Those effects were mediated through the GRs. Conclusions: DEX exerts anti-inflammatory effects on equine peripheral blood neutrophils through both genomic and non-genomic pathways.
Publication Date: 2008-10-17 PubMed ID: 19036458DOI: 10.1016/j.vetimm.2008.10.303Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses the genomic and non-genomic effects of Dexamethasone, a synthetic glucocorticoid, on the function of equine peripheral blood neutrophils, with a focus on its anti-inflammatory capabilities.
Objective and Methodology
- The primary objective of the research is to understand how Dexamethasone (DEX), a potent synthetic glucocorticoid, inhibits the functions of equine peripheral blood neutrophils.
- The researchers used six healthy adult mixed breed female horses for the study.
- To assess the genomic effects of DEX, the researchers isolated peripheral blood neutrophils using a gradient technique and incubated them with LPS and DEX. This mixture was combined with the glucocorticoid receptor (GR) inhibitor RU486.
- The researchers then measured the messenger RNA for inflammation markers IL-8, TNF-alpha, and TLR-4 using real-time RT-PCR.
- The non-genomic effects of DEX were studied by incubating neutrophils with DCF and DEX prior to being stimulated with phorbol myristate acetate.
- To evaluate the contribution of the GR to these effects, neutrophils were co-incubated with DEX and RU486.
- The oxidation of DCF was studied using flow-cytometry.
Results and Conclusions
- It was observed that stimulating neutrophils with LPS resulted in a significant increase in IL-8, TNF-alpha, and TLR-4 mRNA expressions. This process was significantly down-regulated when incubated with DEX.
- DEX also significantly reduced the oxidation of DCF after 10 and 15 minutes of incubation.
- The researchers concluded that these effects were mediated through the GRs.
- The study concluded that DEX exerts anti-inflammatory effects on equine peripheral blood neutrophils through both genomic and non-genomic pathways. This explains its role in controlling inflammation in horses and its application in the treatment of domestic animal species.
Cite This Article
APA
Lecoq L, Vincent P, Lavoie-Lamoureux A, Lavoie JP.
(2008).
Genomic and non-genomic effects of dexamethasone on equine peripheral blood neutrophils.
Vet Immunol Immunopathol, 128(1-3), 126-131.
https://doi.org/10.1016/j.vetimm.2008.10.303 Publication
Researcher Affiliations
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, 3200 Sicotte, Saint-Hyacinthe, Québec, Canada J2S 7C6.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Dactinomycin / pharmacology
- Dexamethasone / pharmacology
- Diffusion Chambers, Culture
- Dose-Response Relationship, Drug
- Female
- Gene Expression Profiling / veterinary
- Gene Expression Regulation / drug effects
- Genomics
- Horses / blood
- Horses / genetics
- Horses / immunology
- Neutrophils / drug effects
- Tetradecanoylphorbol Acetate / pharmacology
Citations
This article has been cited 11 times.- Singh R, Malik P, Kumar M, Kumar R, Alam MS, Mukherjee TK. Secondary fungal infections in SARS-CoV-2 patients: pathological whereabouts, cautionary measures, and steadfast treatments. Pharmacol Rep 2023 Aug;75(4):817-837.
- de Fatima Silva F, Komino ACM, Andreotti S, Boltes Reis G, Caminhotto RO, Landgraf RG, de Souza GO, Sertié RAL, Collins S, Donato J Jr, Bessa Lima F. Dexamethasone-Induced Adipose Tissue Redistribution and Metabolic Changes: Is Gene Expression the Main Factor? An Animal Model of Chronic Hypercortisolism. Biomedicines 2022 Sep 19;10(9).
- Sen S, Singh B, Biswas G. Corticosteroids: A boon or bane for COVID-19 patients?. Steroids 2022 Dec;188:109102.
- Pushparaj K, Kuchi Bhotla H, Arumugam VA, Pappusamy M, Easwaran M, Liu WC, Issara U, Rengasamy KRR, Meyyazhagan A, Balasubramanian B. Mucormycosis (black fungus) ensuing COVID-19 and comorbidity meets - Magnifying global pandemic grieve and catastrophe begins. Sci Total Environ 2022 Jan 20;805:150355.
- Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review. J Vet Intern Med 2021 Jul;35(4):2045-2057.
- Ahmed MH, Hassan A. Dexamethasone for the Treatment of Coronavirus Disease (COVID-19): a Review. SN Compr Clin Med 2020;2(12):2637-2646.
- Wan T, Zhao Y, Fan F, Hu R, Jin X. Dexamethasone Inhibits S. aureus-Induced Neutrophil Extracellular Pathogen-Killing Mechanism, Possibly through Toll-Like Receptor Regulation. Front Immunol 2017;8:60.
- Wang M, Gao P, Wu X, Chen Y, Feng Y, Yang Q, Xu Y, Zhao J, Xie J. Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma. Respir Res 2016 Nov 16;17(1):153.
- Mitre-Aguilar IB, Cabrera-Quintero AJ, Zentella-Dehesa A. Genomic and non-genomic effects of glucocorticoids: implications for breast cancer. Int J Clin Exp Pathol 2015;8(1):1-10.
- Hirsch G, Lavoie-Lamoureux A, Beauchamp G, Lavoie JP. Neutrophils are not less sensitive than other blood leukocytes to the genomic effects of glucocorticoids. PLoS One 2012;7(9):e44606.
- Fugazzola M, Barton AK, Niedorf F, Kietzmann M, Ohnesorge B. Non-genomic action of beclomethasone dipropionate on bronchoconstriction caused by leukotriene C4 in precision cut lung slices in the horse. BMC Vet Res 2012 Sep 10;8:160.
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