title: Resealing of large transmembrane pores produced by streptolysin O in nucleated cells is accompanied by NF-kappaB activation and downstream events.
abstract: 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 kappaB, which thus emerges as a common denominator of stress responses to various pore-forming agents, including alpha-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.
authors.affiliation: Institute of Medical Microbiology, Johannes Gutenberg-University Mainz, D-55101 Mainz, Germany. walev@mail.uni-mainz.de
authors.forename: Iwan
authors.initials: I
authors.lastname: Walev
authors.forename: Michael
authors.initials: M
authors.lastname: Hombach
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Bobkiewicz
authors.forename: Dominic
authors.initials: D
authors.lastname: Fenske
authors.forename: Sucharit
authors.initials: S
authors.lastname: Bhakdi
authors.forename: Matthias
authors.initials: M
authors.lastname: Husmann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D013301:Streptolysins / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D013301:Streptolysins; C025964:streptolysin O; D000255:Adenosine Triphosphate