{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:42:09Z","timestamp":1790008929995,"version":"4.0.1"},"reference-count":43,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2002,2,1]]},"abstract":"<jats:p>Staphylococcus aureus \u03b1-toxin is a pore-forming bacterial exotoxin that has been implicated as a significant virulence factor in human staphylococcal diseases. In primary cultures of rat pneumocyte type II cells and the human A549 alveolar epithelial cell line, purified \u03b1-toxin provoked rapid-onset phosphatidylinositol (PtdIns) hydrolysis as well as liberation of nitric oxide and the prostanoids PGE<jats:sub>2<\/jats:sub>, PGI<jats:sub>2<\/jats:sub>, and thromboxane A<jats:sub>2<\/jats:sub>. In addition, sustained upregulation of proinflammatory interleukin (IL)-8 mRNA expression and protein secretion occurred. \u201cPriming\u201d with low-dose IL-1\u03b2 markedly enhanced the IL-8 response to \u03b1-toxin, which was then accompanied by IL-6 appearance. The cytokine response was blocked by the intracellular Ca<jats:sup>2+<\/jats:sup>-chelating reagent 1,2-bis(2-aminophenoxy)-ethane- N,N,N\u2032 ,N\u2032-tetraacetic acid, the protein kinase C inhibitor bis-indolyl maleimide I, as well as two independent inhibitors of nuclear factor-\u03baB activation, pyrrolidine dithiocarbamate and caffeic acid phenethyl ester. We conclude that alveolar epithelial cells are highly reactive target cells of staphylococcal \u03b1-toxin. \u03b1-Toxin pore-associated transmembrane Ca<jats:sup>2+<\/jats:sup>flux and PtdIns hydrolysis-related signaling with downstream activation of protein kinase C and nuclear translocation of nuclear factor-\u03baB are suggested to represent important underlying mechanisms. Such reactivity of the alveolar epithelial cells may be relevant for pathogenic sequelae in staphylococcal lung disease.<\/jats:p>","DOI":"10.1152\/ajplung.00156.2001","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:15:53Z","timestamp":1425413753000},"page":"L207-L214","source":"Crossref","is-referenced-by-count":57,"title":["Mediator generation and signaling events in alveolar epithelial cells attacked by<i>S. aureus<\/i>\u03b1-toxin"],"prefix":"10.1152","volume":"282","author":[{"given":"Frank","family":"Rose","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Justus-Liebig University, Giessen D-35392, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Dahlem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Justus-Liebig University, Giessen D-35392, 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