An Update on NLRP3 Inflammasome Activation by Engineered Nanomaterials

Author(s): Rob J. Vandebriel, Susan Dekkers, Wim H de Jong, Flemming R. Cassee

Journal Name: Current Bionanotechnology (Discontinued)

Volume 2 , Issue 1 , 2016

Graphical Abstract:


The widespread and increasing use of engineered nanomaterials (ENMs) increases the risk of exposure by human beings. This notion has generated concern that ENMs may give rise to adverse health effects. Toxicity of ENMs is determined by both physical aspects and chemical composition. The immune system may respond to ENMs, amongst others by inflammatory reactions. Among the mechanisms underlying inflammation, inflammasome activation (especially the NLRP3 inflammasome) has drawn significant attention because it can be induced by a wide range of stimuli including ENMs and it is associated with various inflammatory diseases, including lung fibrosis, obesity and type 2 diabetes. Inflammasomes are intracellular multiprotein complexes that assemble upon stimulation, resulting in the activation of caspase-1 that in turn induces the production of interleukin (IL)-1β and IL-18. These cytokines are potent mediators of inflammation. This review summarizes the literature on NLRP3 inflammasome activation by ENMs published between 2013 and 2015. Newly identified mechanisms include a role for Endoplasmic Reticulum stress in NLRP3 inflammasome activation by Ag and ZnO ENMs and an initiating role for IL-1. Novel insights in surface functionalization with the aim of reducing NLRP3 inflammasome activation were obtained. In vitro assays for NLRP3 inflammasome activation may predict in vivo fibrogenic potency of ENMs; including such an assay in a test battery for hazard identification is advised.

Keywords: Engineered nanomaterial, NLRP3, inflammasome, inflammation, fibrosis, ER stress, surface functionalization, IL- 1alpha, IL-1beta, IL-18, caspase-1.

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Article Details

Year: 2016
Published on: 20 June, 2016
Page: [40 - 46]
Pages: 7
DOI: 10.2174/2213529402666160601122127

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