{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:35:34Z","timestamp":1773693334491,"version":"3.50.1"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"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":[[2008,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Impaired host defenses and vascular dysfunction are hallmarks of the late, antibiotic-refractory stages of systemic anthrax infection. Anthrax lethal toxin (LT), a key virulence factor of Bacillus anthracis, was previously shown to enhance VCAM-1 expression on primary human endothelial cells suggesting a causative link between dysregulated adhesion molecule expression and the poor immune response and vasculitis associated with anthrax. In this study, we report that LT amplification of TNF-induced VCAM-1 expression is driven transcriptionally by the cooperative activation of NF-\u03baB and IFN regulatory factor-1 (IRF-1). LT enhancement of NF-\u03baB phosphorylation and nuclear translocation correlated temporally with a delayed reaccumulation of I\u03baB\u03b1, while increased induction of IRF-1 was linked to STAT1 activation. LT failed to augment TNF-induced ICAM-1 or E-selectin expression, two adhesion molecules regulated by NF-\u03baB, but not IRF-1. These results suggest that LT can differentially modulate NF-\u03baB target genes and highlight the importance of IRF-1 in VCAM-1 enhancement. Altering the activity of key transcription factors involved in host response to infection may be a critical mechanism by which LT contributes to anthrax pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.180.11.7516","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:57Z","timestamp":1397862597000},"page":"7516-7524","source":"Crossref","is-referenced-by-count":26,"title":["Anthrax Lethal Toxin Enhances TNF-Induced Endothelial VCAM-1 Expression via an IFN Regulatory Factor-1-Dependent Mechanism"],"prefix":"10.1093","volume":"180","author":[{"given":"Jason M","family":"Warfel","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration , Bethesda, MD 20892"},{"name":"Department of Microbiology and Immunology, Georgetown University Medical Center , Washington, DC 20057"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felice","family":"D\u2019Agnillo","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"2025032701443780300_R1","first-page":"19","volume-title":"Curr. 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