Characterization of equine inflammasomes and their regulation
Characterization of equine inflammasomes and their regulation
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DOI：
10.1007/s11259-020-09772-1
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发表时间：
2020-04-15
影响因子：
2.2
通讯作者：
Lee, Geun-Shik
中科院分区：
文献类型：
--
作者：
Ahn, Huijeong;Kim, Jeongeun;Lee, Geun-Shik
炎症体是一种细胞质的多蛋白复合体，它是对细胞内致病和内源性危险信号的反应，随后激活caspase-1，使白细胞介素1-β等前体细胞因子成熟。大多数炎症体研究都是在人类和啮齿动物身上进行的，而兽医物种中的炎症体还没有得到很好的描述。在这项研究中，我们观察了众所周知的炎症体激活剂对马外周血单核细胞(PBMC)的影响。NLRP3炎症小体的触发物包括三磷酸腺苷、黑素、铝晶体和尿酸单钠晶体，NLRP3激活以剂量依赖的方式诱导IL-1β的分泌。NLRC4和AIM2炎性小体的激活剂包括胞质鞭毛蛋白和dsDNA，它们的激活诱导IL-1β的分泌。细菌炎症小体触发了鼠伤寒沙门氏菌和单核细胞增多性李斯特菌，也诱导了IL-β的释放。为了阐明钾外流作为NLRP3炎性小体激活的上游信号的作用，在NLRP3触发剂存在的情况下，用钾外流阻断剂处理马外周血单个核细胞。因此，抑制钾外流并不能完全抑制马NLRP3炎性小体激活产生的IL-1β的分泌。综上所述，这些结果表明，马的PBMC通常会在已知的炎症体激活剂的作用下分泌IL-1β，尽管马的NLRP3炎症体的激活可能不依赖于钾的外流。
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.