Characterization of equine inflammasomes and their regulation

초록

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)-1 beta. 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-1 beta secretion in a dose-dependent manner. Activators of NLRC4 and AIM2 inflammasomes include cytosolic flagellin and dsDNA, and their activation induces IL-1 beta secretion. The bacterial inflammasome triggers Salmonella Typhimurium and Listeria monocytogenes also induce IL-beta 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-1 beta 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-1 beta in response to well-known inflammasome activators, although equine NLRP3 inflammasome activation might not be dependent on potassium efflux.

키워드