{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:24:34Z","timestamp":1778826274583,"version":"3.51.4"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"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":[[2011,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Anthrax lethal toxin (LeTx) is a virulence factor of Bacilillus anthracis that is a bivalent toxin, containing lethal factor (LF) and protective Ag proteins, which causes cytotoxicity and altered macrophage function. LeTx exposure results in early K+ efflux from macrophages associated with caspase-1 activation and increased IL-1\u03b2 release. The mechanism of this toxin-induced K+ efflux is unknown. The goals of the current study were to determine whether LeTx-induced K+ efflux from macrophages is mediated by toxin effects on specific K+ channels and whether altered K+-channel activity is involved in LeTx-induced IL-1\u03b2 release. Exposure of macrophages to LeTx induced a significant increase in the activities of two types of K+ channels that have been identified in mouse macrophages: Ba2+-sensitive inwardly rectifying K+ (Kir) channels and 4-aminopyridine\u2013sensitive outwardly rectifying voltage-gated K+ (Kv) channels. LeTx enhancement of both Kir and Kv required the proteolytic activity of LF, because exposure of macrophages to a mutant LF-protein (LFE687C) combined with protective Ag protein had no effect on the currents. Furthermore, blocking Kir and Kv channels significantly decreased LeTx-induced release of IL-1\u03b2. In addition, retroviral transduction of macrophages with wild-type Kir enhanced LeTx-induced release of IL-1\u03b2, whereas transduction of dominant-negative Kir blocked LeTx-induced release of IL-1\u03b2. Activation of caspase-1 was not required for LeTx-induced activation of either of the K+ channels. These data indicate that a major mechanism through which LeTx stimulates macrophages to release IL-1\u03b2 involves an LF-protease effect that enhances Kir and Kv channel function during toxin stimulation.<\/jats:p>","DOI":"10.4049\/jimmunol.1001078","type":"journal-article","created":{"date-parts":[[2011,3,20]],"date-time":"2011-03-20T00:13:32Z","timestamp":1300580012000},"page":"5236-5243","source":"Crossref","is-referenced-by-count":13,"title":["Anthrax Lethal Factor Activates K+ Channels To Induce IL-1\u03b2 Secretion in Macrophages"],"prefix":"10.1093","volume":"186","author":[{"given":"Johnson","family":"Thomas","sequence":"first","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Epshtein","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Chopra","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"},{"name":"Section of Infectious Diseases, Immunology and International Medicine, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balazs","family":"Ordog","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute , Montreal, Quebec H1T 1C8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmood","family":"Ghassemi","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Immunology and International Medicine, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W","family":"Christman","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute , Montreal, Quebec H1T 1C8 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L","family":"Cook","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Immunology and International Medicine, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"},{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Levitan","sequence":"additional","affiliation":[{"name":"Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,5,1]]},"reference":[{"key":"2025032411243740100_r1","doi-asserted-by":"crossref","first-page":"4549","DOI":"10.1128\/IAI.68.8.4549-4558.2000","article-title":"Attenuated nontoxinogenic and nonencapsulated recombinant Bacillus anthracis spore vaccines protect against anthrax","volume":"68","author":"Cohen","year":"2000","journal-title":"Infect. 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