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Infection and Immunity, April 2001, p. 2630-2635, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2630-2635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Y. Dragneva,1 C. D. Anuradha,1 A. Valeva,1 A. Hoffmann,2 S. Bhakdi,1 and M. Husmann1,*

Institute of Medical Microbiology and Hygiene, University of Mainz, Mainz, Germany,1 and California Institute of Technology, Pasadena, California2

Received 6 October 2000/Returned for modification 16 November 2000/Accepted 18 January 2001

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.

* Corresponding author. Mailing address: Institute of Medical Microbiology and Hygiene, University of Mainz, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany. Phone: 49 (6131) 39-33128. Fax: 49 (6131) 39-32359. E-mail: MattHusmann{at}web.de.

Infection and Immunity, April 2001, p. 2630-2635, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2630-2635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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