Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei, 066004, China.
Inflammation. 2014 Apr;37(2):457-66. doi: 10.1007/s10753-013-9759-z.
Exposure to nickel (Ni(2+)) can trigger allergic reactions in susceptible individuals, which is widely accepted as the major cause of allergic contact hypersensitivity (CHS) worldwide. Although Ni(2+)-induced proinflammatory responses clearly play a pivotal role in CHS, the underlying molecular mechanism has not been fully defined. Here we report that Ni(2+) activates the NLRP3-ASC-caspase-1 immune signaling pathway in antigen-presenting cells, leading to the proteolytic processing and secretion of a proinflammatory cytokine, interleukin-1β (IL-1β). The activation of this signaling axis is independent of phagolysosome-cathepsin B pathway. Instead, Ni(2+) induces mitochondrial reactive oxygen species accumulation and cation fluxes, both of which are required for activating the NLRP3-ASC-caspase-1 pathway. Together, these results identified a novel innate immune signaling pathway (NLRP3-ASC-caspase-1-IL-1β) activated by Ni(2+) and provided a mechanistic basis for optimizing the therapeutic intervention against Ni(2+)-induced allergy in patients.
镍（Ni(2+))暴露会引发易感个体的过敏反应，这被广泛认为是全球过敏性接触超敏反应（CHS）的主要原因。尽管 Ni(2+)-诱导的促炎反应显然在 CHS 中起着关键作用，但潜在的分子机制尚未完全确定。在这里，我们报告 Ni(2+)在抗原呈递细胞中激活 NLRP3-ASC-半胱天冬酶-1 免疫信号通路，导致促炎细胞因子白细胞介素-1β（IL-1β）的蛋白水解加工和分泌。该信号轴的激活不依赖于吞噬溶酶体组织蛋白酶 B 途径。相反，Ni(2+)诱导线粒体活性氧物质的积累和阳离子通量，这两者对于激活 NLRP3-ASC-半胱天冬酶-1 途径都是必需的。总之，这些结果确定了一种由 Ni(2+)激活的新型先天免疫信号通路（NLRP3-ASC-半胱天冬酶-1-IL-1β），并为优化针对 Ni(2+)-诱导过敏的治疗干预提供了机制基础。
