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Nickel Induces Interleukin-1β Secretion via the NLRP3–ASC–Caspase-1 Pathway

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Abstract

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-1β (IL-1β). 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-1β) activated by Ni2+ and provided a mechanistic basis for optimizing the therapeutic intervention against Ni2+-induced allergy in patients.

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Acknowledgments

We thank Dr. Katherine Fitzgerald (from University of Massachusetts Medical School, USA) for providing immortalized inflammasome-deficient macrophages. This work is supported by the National Natural Science Foundation of China (31140093) and Natural Science Foundation of Hebei Province (C2013204130).

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Biotechnology, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei, 066004, China

    Xiujin Li

  2. Laboratory of Molecular Virology and Immunology, College of Veterinary Medicine, Agricultural University of Hebei, Baoding, 071001, China

    Fei Zhong

  3. Hebei Engineering and Technology Research Center of Veterinary Biological Products, Agricultural University of Hebei, Baoding, 071001, China

    Fei Zhong

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  1. Xiujin Li
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  2. Fei Zhong
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Correspondence to Fei Zhong.

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Li, X., Zhong, F. Nickel Induces Interleukin-1β Secretion via the NLRP3–ASC–Caspase-1 Pathway. Inflammation 37, 457–466 (2014). https://doi.org/10.1007/s10753-013-9759-z

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  • DOI: https://doi.org/10.1007/s10753-013-9759-z

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