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Veterinary research communications2020; 44(2); 51-59; doi: 10.1007/s11259-020-09772-1

Characterization of equine inflammasomes and their regulation.

Abstract: Inflammasome, a cytosolic multi-protein complex, assembly is a response to sensing intracellular pathogenic and endogenic danger signals followed by caspase-1 activation, which maturates precursor cytokines such as interleukin (IL)-1β. Most inflammasome research has been undertaken in humans and rodents, and inflammasomes in veterinary species have not been well-characterized. In this study, we observed the effects of well-known inflammasome activators on equine peripheral blood monocytes (PBMCs). The NLRP3 inflammasome triggers include ATP, nigericin, aluminum crystals, and monosodium urate crystals, and NLRP3 activation induces IL-1β secretion in a dose-dependent manner. Activators of NLRC4 and AIM2 inflammasomes include cytosolic flagellin and dsDNA, and their activation induces IL-1β secretion. The bacterial inflammasome triggers Salmonella Typhimurium and Listeria monocytogenes also induce IL-β releases. To elucidate the role of potassium efflux as an upstream signal of NLRP3 inflammasome activation, equine PBMCs were treated with blockers of potassium efflux in the presence of NLRP3 triggers. As a result, the IL-1β secretion stemming from equine NLRP3 inflammasome activation was not completely attenuated by the inhibition of potassium efflux. Taken together, the results indicate that equine PBMCs normally secrete IL-1β in response to well-known inflammasome activators, although equine NLRP3 inflammasome activation might not be dependent on potassium efflux.
Publication Date: 2020-04-15 PubMed ID: 32297137DOI: 10.1007/s11259-020-09772-1Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper examines the functioning and regulation of equine inflammasomes – a cluster of proteins in horses that trigger inflammation in response to disease-causing organisms and other threats. The study particularly investigates the aspects of inflammasome activation and how various triggers might induce the secretion of an important immune response molecule called interleukin (IL)-1β.

Understanding Inflammasomes and the Study

  • Equine inflammasomes are a cluster of proteins found in horses. These proteins assemble in response to pathogenic (disease-caiving) and endogenic (internal) danger signals, leading to the activation of a protein called caspase-1.
  • Caspase-1 maturation leads to cytokines such as interleukin (IL)-1β. Cytokines can be understood as substances secreted by certain cells of the immune system that have an effect on other cells, in this case, resulting in inflammation.
  • However, most of the research on inflammasomes has been conducted on humans and rodents, leaving a gap of knowledge when it comes to veterinary species like horses. This study attempts to fill that gap.

Activators and Effect on Equine Peripheral Blood Monocytes (PBMCs)

  • The research observed the effects of known inflammasome activators on equine PBMCs. These include ATP, nigericin, aluminum crystals, and monosodium urate crystals for NLRP3 inflammasome; cytosolic flagellin and dsDNA for NLRC4 and AIM2 inflammasomes; and certain bacteria’s like Salmonella Typhimurium and Listeria monocytogenes.
  • The activation of these inflammasomes lead to the secretion of IL-1β in a dose-dependent manner, meaning the amount of secretion increases with the increase in the dose of the activator.

Role of Potassium Efflux

  • Potassium efflux (outward flow of potassium ions) is traditionally considered an upstream signal that precedes NLRP3 inflammasome activation. The study examined this relationship in horse PBMCs.
  • While treating equine PBMCs with blockers of potassium efflux in the presence of NLRP3 triggers, it was observed that the IL-1β secretion from the activation of NLRP3 inflammasome did not completely stop.
  • These results suggest that the activation of the equine NLRP3 inflammasome, unlike in other organisms, might not be dependent on potassium efflux.

In summary, this study contributes to the understanding of the functioning and regulation of inflammasomes in equines and could potentially influence the course of veterinary medical research and treatment methodologies.

Cite This Article

APA
Ahn H, Kim J, Lee H, Lee E, Lee GS. (2020). Characterization of equine inflammasomes and their regulation. Vet Res Commun, 44(2), 51-59. https://doi.org/10.1007/s11259-020-09772-1

Publication

ISSN: 1573-7446
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 44
Issue: 2
Pages: 51-59

Researcher Affiliations

Ahn, Huijeong
  • College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341, Chuncheon, Republic of Korea.
Kim, Jeongeun
  • College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341, Chuncheon, Republic of Korea.
Lee, Hansae
  • College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341, Chuncheon, Republic of Korea.
Lee, Eunsong
  • College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341, Chuncheon, Republic of Korea.
Lee, Geun-Shik
  • College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341, Chuncheon, Republic of Korea. leegeun@kangwon.ac.kr.
  • Laboratory of Inflammatory Diseases, Department of Physiology, College of Veterinary Medicine, Kangwon National University, 24341, Chuncheon, Republic of Korea. leegeun@kangwon.ac.kr.

MeSH Terms

  • Adenosine Triphosphate / pharmacology
  • Aluminum / pharmacology
  • Animals
  • DNA / pharmacology
  • Flagellin / pharmacology
  • Horses / immunology
  • Inflammasomes / drug effects
  • Inflammasomes / immunology
  • Interleukin-1beta / immunology
  • Listeria monocytogenes / immunology
  • Monocytes / immunology
  • Nigericin / pharmacology
  • Salmonella typhimurium / immunology
  • Uric Acid / pharmacology

Grant Funding

  • NRF-2018R1A2B2004097 / National Research Foundation of Korea
  • NRF-2018R1D1A1B07048337 / National Research Foundation of Korea

Citations

This article has been cited 7 times.
  1. Carnet F, Perrin-Cocon L, Paillot R, Lotteau V, Pronost S, Vidalain PO. An inventory of adjuvants used for vaccination in horses: the past, the present and the future. Vet Res 2023 Mar 2;54(1):18.
    doi: 10.1186/s13567-023-01151-3pubmed: 36864517google scholar: lookup
  2. Ahn H, Lee G, Han BC, Lee SH, Lee GS. Maltol, a Natural Flavor Enhancer, Inhibits NLRP3 and Non-Canonical Inflammasome Activation. Antioxidants (Basel) 2022 Sep 28;11(10).
    doi: 10.3390/antiox11101923pubmed: 36290645google scholar: lookup
  3. Suagee-Bedore J, Shost N, Miller C, Grado L, Bechelli J. Age and Body Condition Influence the Post-Prandial Interleukin-1β Response to a High-Starch Meal in Horses. Animals (Basel) 2021 Nov 24;11(12).
    doi: 10.3390/ani11123362pubmed: 34944138google scholar: lookup
  4. Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W. Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses. Animals (Basel) 2021 Nov 13;11(11).
    doi: 10.3390/ani11113247pubmed: 34827979google scholar: lookup
  5. Ahn H, Lee G, Lee GS. Lower Temperatures Exacerbate NLRP3 Inflammasome Activation by Promoting Monosodium Urate Crystallization, Causing Gout. Cells 2021 Jul 29;10(8).
    doi: 10.3390/cells10081919pubmed: 34440688google scholar: lookup
  6. Ahn H, Jeong DH, Lee G, Lee SJ, Yang JJ, Kim YH, Hahn TW, Choi S, Lee GS. Characterization of Inflammasomes and Their Regulation in the Red Fox. Animals (Basel) 2023 Dec 13;13(24).
    doi: 10.3390/ani13243842pubmed: 38136879google scholar: lookup
  7. Reißmann M, Rajavel A, Kokov ZA, Schmitt AO. Identification of Differentially Expressed Genes after Endurance Runs in Karbadian Horses to Determine Candidates for Stress Indicators and Performance Capability. Genes (Basel) 2023 Oct 24;14(11).
    doi: 10.3390/genes14111982pubmed: 38002925google scholar: lookup