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Resealing of large transmembrane pores produced by streptolysin O in nucleated cells is accompanied by NF‐κB activation and downstream events
Author(s) -
Walev Iwan,
Hombach Michael,
Bobkiewicz Wieslawa,
Fenske Dominic,
Bhakdi Sucharit,
Husmann Matthias
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0572fje
Subject(s) - cytolysin , streptolysin , microbiology and biotechnology , transmembrane protein , paracrine signalling , chemistry , cytokine , transcription factor , biophysics , biology , receptor , immunology , biochemistry , gene , virulence , bacterial protein
Streptolysin O (SLO), archetype of a cholesterol‐binding bacterial cytolysin, forms large pores in the plasma membrane of mammalian cells. We have recently reported that when a limited number of pores are generated in a cell, they can be sealed in a Ca ++ ‐dependent process. Here, we show that resealing is followed by the release of IL‐6 and IL‐8 from keratinocytes and from endothelial cells, both relevant targets for SLO attack. Production of cytokines by these cells was preceded by activation of transcription factor nuclear factor κB, which thus emerges as a common denominator of stress responses to various pore‐forming agents, including α‐toxin of Staphylococcus aureus and complement. Furthermore, we show that activation and cytokine release in response to an agent that forms a pore in the plasma membrane do not depend on paracrine effects, because supernatants of cells perforated by SLO did not activate bystander cells. The study provides definitive evidence that a transient transmembrane pore suffices to trigger productive transcriptional activation in a target cell.