Arsenic trioxide and other arsenical compounds inhibit the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes.

ABSTRACT: Inflammasomes are large cytoplasmic multiprotein complexes that activate caspase-1 in response to diverse intracellular danger signals. Inflammasome components termed nucleotide-binding oligomerization domain-like receptor (NLR) proteins act as sensors for pathogen-associated molecular patterns, stress, or danger stimuli. We discovered that arsenicals, including arsenic trioxide and sodium arsenite, inhibited activation of the NLRP1, NLRP3, and NAIP5/NLRC4 inflammasomes by their respective activating signals, anthrax lethal toxin, nigericin, and flagellin. These compounds prevented the autoproteolytic activation of caspase-1 and the processing and secretion of IL-1β from macrophages. Inhibition was independent of protein synthesis induction, proteasome-mediated protein breakdown, or kinase

SUBMITTER: Maier NK 

PROVIDER: S-EPMC3884817 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature