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Subcytocidal Attack by Staphylococcal Alpha-Toxin Activates NF-κB and Induces Interleukin-8 Production

Dragneva, Y. and Anuradha, C. D. and Valeva, A. and Hoffmann, A. and Bhakdi, S. and Husmann, M. (2001) Subcytocidal Attack by Staphylococcal Alpha-Toxin Activates NF-κB and Induces Interleukin-8 Production. Infection and Immunity, 69 (4). pp. 2630-2635. ISSN 0019-9567. PMCID PMC98200.

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Formation of transmembrane pores by staphylococcal alpha-toxin can provoke a spectrum of events depending on target cell species and toxin dose, and in certain cases, repair of the lesions has been observed. Here, we report that transcriptional processes are activated as a response of cells to low toxin doses. Exposure of monocytic (THP-1) or epithelial (ECV304) cells to 40 to 160 ng/ml alpha-toxin provoked a drop in cellular ATP level that was followed by secretion of substantial amounts of interleukin-8 (IL-8). Cells transfected with constructs comprising the proximal IL-8 promoter fused to luciferase or to green fluorescent protein cDNA exhibited enhanced reporter gene expression following toxin treatment. Electrophoretic mobility shift and immunofluorescence assays demonstrated that IL-8 secretion was preceded by activation of NF-kappa B. Transfection experiments conducted with p65/p50 double-deficient cells showed that activation of the IL-8 promoter/reporter by toxin was absolutely dependent on NF-kappa B. In contrast, this transcription factor was not required for lesion repair. Attack of cells by low doses of a pore-forming toxin can lead to transcriptional gene activation, which is followed by production of mediators that may contribute to the initiation and propagation of inflammatory lesions.

Item Type:Article
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URLURL TypeDescription CentralArticle
Alternate Title:Subcytocidal Attack by Staphylococcal Alpha-Toxin Activates NF-kappa B and Induces Interleukin-8 Production
Additional Information:© 2001, American Society for Microbiology. Received 6 October 2000/Returned for modification 16 November 2000/Accepted 18 January 2001 This work was supported by the Deutsche Forschungsgemeinschaft (SFB 490) and the Verband der Chemischen Industrie.
Funding AgencyGrant Number
Deutsche Forschungsgemeinschaft (DFG)SFB 490
Verband der Chemischen IndustrieUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC98200
Record Number:CaltechAUTHORS:DRAiai01
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Official Citation:Subcytocidal Attack by Staphylococcal Alpha-Toxin Activates NF-κB and Induces Interleukin-8 Production Y. Dragneva, C. D. Anuradha, A. Valeva, A. Hoffmann, S. Bhakdi, M. Husmann Infection and Immunity Apr 2001, 69 (4) 2630-2635; DOI: 10.1128/IAI.69.4.2630-2635.2001
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2723
Deposited By: Archive Administrator
Deposited On:24 Apr 2006
Last Modified:02 Oct 2019 22:56

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