科研之友
微信
新浪微博
Facebook
分享链接
摘要
Exposure to nickel (Ni2+) can trigger allergic reactions in susceptible individuals, which is widely accepted as the major cause of allergic contact hypersensitivity (CHS) worldwide. Although Ni2+-induced proinflammatory responses clearly play a pivotal role in CHS, the underlying molecular mechanism has not been fully defined. Here we report that Ni2+ 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-1 beta (IL-1 beta). The activation of this signaling axis is independent of phagolysosome-cathepsin B pathway. Instead, Ni2+ 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-1 beta) activated by Ni2+ and provided a mechanistic basis for optimizing the therapeutic intervention against Ni2+-induced allergy in patients.
