{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:26:30Z","timestamp":1789982790002,"version":"4.0.1"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inflammasomes are large cytoplasmic multiprotein complexes that activate caspase-1 in response to diverse intracellular danger signals. Inflammasome components termed nucleotide-binding oligomerization domain\u2013like 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-1\u03b2 from macrophages. Inhibition was independent of protein synthesis induction, proteasome-mediated protein breakdown, or kinase signaling pathways. Arsenic trioxide and sodium arsenite did not directly modify or inhibit the activity of preactivated recombinant caspase-1. Rather, they induced a cellular state inhibitory to both the autoproteolytic and substrate cleavage activities of caspase-1, which was reversed by the reactive oxygen species scavenger N-acetylcysteine but not by reducing agents or NO pathway inhibitors. Arsenicals provided protection against NLRP1-dependent anthrax lethal toxin\u2013mediated cell death and prevented NLRP3-dependent neutrophil recruitment in a monosodium urate crystal inflammatory murine peritonitis model. These findings suggest a novel role in inhibition of the innate immune response for arsenical compounds that have been used as therapeutics for a few hundred years.<\/jats:p>","DOI":"10.4049\/jimmunol.1301434","type":"journal-article","created":{"date-parts":[[2013,12,14]],"date-time":"2013-12-14T03:19:59Z","timestamp":1386991199000},"page":"763-770","source":"Crossref","is-referenced-by-count":57,"title":["Arsenic Trioxide and Other Arsenical Compounds Inhibit the NLRP1, NLRP3, and NAIP5\/NLRC4 Inflammasomes"],"prefix":"10.1093","volume":"192","author":[{"given":"Nolan K","family":"Maier","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devorah","family":"Crown","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine, National Heart Lung and Blood Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H","family":"Leppla","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Moayeri","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,15]]},"reference":[{"key":"2025032404073106700_r1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.immunol.021908.132715","article-title":"The inflammasomes: guardians of the body","volume":"27","author":"Martinon","year":"2009","journal-title":"Annu. 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