Characterization of equine inflammasomes and their regulation

Vet Res Commun. 2020 May;44(2):51-59. doi: 10.1007/s11259-020-09772-1. Epub 2020 Apr 15.

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.

Keywords: Cytokine; Equus ferus caballus; Horse; Inflammasome; Interleukin-1β.

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

Substances

  • Inflammasomes
  • Interleukin-1beta
  • Flagellin
  • Uric Acid
  • Adenosine Triphosphate
  • DNA
  • Aluminum
  • Nigericin