{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:42:31Z","timestamp":1791121351590,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Anthrax lethal toxin (LT) activates the NLRP1b (NALP1b) inflammasome and caspase-1 in macrophages from certain inbred mouse strains, but the mechanism by which this occurs is poorly understood. We report here that similar to several NLRP3 (NALP3, cryopyrin)-activating stimuli, LT activation of the NLRP1b inflammasome involves lysosomal membrane permeabilization (LMP) and subsequent cytoplasmic cathepsin B activity. CA-074Me, a potent cathepsin B inhibitor, protects LT-sensitive macrophages from cell death and prevents the activation of caspase-1. RNA interference knockdown of cathepsin B expression, however, cannot prevent LT-mediated cell death, suggesting that CA-074Me may also act on other cellular proteases released during LMP. CA-074Me appears to function downstream of LT translocation to the cytosol (as assessed by mitogen-activated protein kinase kinase cleavage), K\n            <jats:sup>+<\/jats:sup>\n            effluxes, and proteasome activity. The initial increase in cytoplasmic activity of cathepsin B occurs at the same time or shortly before caspase-1 activation but precedes a larger-scale lysosomal destabilization correlated closely with cytolysis. We present results suggesting that LMP may be involved in the activation of the NLRP1b inflammasome.\n          <\/jats:p>","DOI":"10.1128\/iai.00730-09","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T01:10:28Z","timestamp":1248743428000},"page":"4327-4336","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":70,"title":["CA-074Me Protection against Anthrax Lethal Toxin"],"prefix":"10.1128","volume":"77","author":[{"given":"Zachary L.","family":"Newman","sequence":"first","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Leppla","sequence":"additional","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Moayeri","sequence":"additional","affiliation":[{"name":"Bacterial Toxins and Therapeutics Section, Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200312072"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.1.2283"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308558101"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000140272.54583.FB"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301911200"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7306(09)60020-X"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.310"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1724"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(97)00007-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(92)90290-D"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707370105"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.5.999"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1703"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.245-252.1993"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-033597"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103150200"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00716-06"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1636"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03403527"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401264"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1631"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202568200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"C1100","DOI":"10.1152\/ajpcell.00494.2003","volume":"286","year":"2004","unstructured":"Kahlenberg, J. 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