Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation.
Huijeong AhnJeongeun KimSeung Goo KangSung-Il YoonHyun-Jeong KoPyeung-Hyeun KimEui-Ju HongBeum-Soo AnEunsong LeeGeun-Shik LeePublished in: Scientific reports (2018)
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.
Keyphrases
- heavy metals
- nlrp inflammasome
- risk assessment
- health risk assessment
- health risk
- mitochondrial dna
- reactive oxygen species
- sewage sludge
- drinking water
- copy number
- oxidative stress
- inflammatory response
- transcription factor
- cell death
- small molecule
- type diabetes
- gene expression
- signaling pathway
- combination therapy
- insulin resistance
- long non coding rna
- genome wide
- case control