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Sci Rep. 2018 Sep 12;8(1):13659. doi: 10.1038/s41598-018-31717-7.

Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation.

Author information

1
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
2
Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
3
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
4
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
5
College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, Republic of Korea.
6
Department of Biomaterial Science, College of Natural Resources and Life Science, Pusan National University, Gyeongsangnam-do, 50612, Republic of Korea.
7
College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea. leegeun@kangwon.ac.kr.

Abstract

Exposure to heavy metals can cause several diseases associated with the immune system. Although the effects of heavy metals on production of inflammatory cytokines have been previously studied, the role of heavy metals in inflammasome activation remains poorly studied. The inflammasome is an intracellular multi-protein complex that detects intracellular danger signals, resulting in inflammatory responses such as cytokine maturation and pyroptosis. In this study, we elucidated the effects of four heavy metals, including cadmium (Cd), mercury (Hg), arsenic (As), and lead (Pb), on the activation of NLRP3, NLRC4, and AIM2 inflammasomes. In our results, mercury and arsenic inhibited interleukin (IL)-1β and IL-18 secretion resulting from canonical and non-canonical NLRP3 inflammasome activation in macrophages and attenuated elevation of serum IL-1β in response to LPS treatment in mice. In the mechanical studies, mercury interrupted production of mitochondrial reactive oxygen species, release of mitochondrial DNA, and activity of recombinant caspase-1, whereas arsenic down-regulated expression of promyelocytic leukemia protein. Both mercury and arsenic inhibited Asc pyroptosome formation and gasdermin D cleavage. Thus, we suggest that exposure to mercury and/or arsenic could disrupt inflammasome-mediated inflammatory responses, which might cause unexpected side effects.

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