Characterization of equine inflammasomes and their regulation
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ORIGINAL ARTICLE
Characterization of equine inflammasomes and their regulation Huijeong Ahn 1 & Jeongeun Kim 1 & Hansae Lee 1 & Eunsong Lee 1 & Geun-Shik Lee 1,2 Received: 9 December 2019 / Accepted: 31 March 2020 # Springer Nature B.V. 2020
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. Keyword Horse . Equus ferus caballus . Inflammasome . Cytokine . Interleukin-1β
Introduction Cytosolic pathogen- and damage-associated molecular pattern molecules (PAMPs and DAMPs) lead to the assembly of inflammasomes, multi-protein complexes in myeloid and epithelial cells, which activate caspase-1 to maturate interleukin (IL)-1β and IL-18. Inflammasomes have been implicated in the pathogenesis of a wide range of diseases in humans and mice, and they have been investigated as potential therapeutic targets in attempts to cure those diseases (Swanson et al. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11259-020-09772-1) contains supplementary material, which is available to authorized users. * Geun-Shik Lee [email protected] 1
College of Veterinary Medicine, Institute of Veterinary Science, Kangwon National University, 24341 Chuncheon, Republic of Korea
2
Laboratory of Inflammatory Diseases, Department of Physiology, College of Veterinary Medicine, Kangwon National University, 24341 Chuncheon, Republic of Korea
2019). Initially inflammasomes were simply known as regulators of the secretion of IL-1β and IL-18 through caspase-1 activation in innate immune cells, but it has been recently reported that they are active in governing between innate and adap
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