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Infection and Immunity, April 2001, p. 2630-2635, Vol. 69, No. 4
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-
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-
B and Induces Interleukin-8
Production
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-
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.
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