PMID- 11792625
OWN - NLM
STAT- MEDLINE
DCOM- 20020307
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 282
IP  - 2
DP  - 2002 Feb
TI  - Mediator generation and signaling events in alveolar epithelial cells attacked by 
      S. aureus alpha-toxin.
PG  - L207-14
AB  - Staphylococcus aureus alpha-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 alpha-toxin provoked rapid-onset 
      phosphatidylinositol (PtdIns) hydrolysis as well as liberation of nitric oxide 
      and the prostanoids PGE(2), PGI(2), and thromboxane A(2). In addition, sustained 
      upregulation of proinflammatory interleukin (IL)-8 mRNA expression and protein 
      secretion occurred. "Priming" with low-dose IL-1beta markedly enhanced the IL-8 
      response to alpha-toxin, which was then accompanied by IL-6 appearance. The 
      cytokine response was blocked by the intracellular Ca(2+)-chelating reagent 
      1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, the protein kinase C 
      inhibitor bis-indolyl maleimide I, as well as two independent inhibitors of 
      nuclear factor-kappaB activation, pyrrolidine dithiocarbamate and caffeic acid 
      phenethyl ester. We conclude that alveolar epithelial cells are highly reactive 
      target cells of staphylococcal alpha-toxin. alpha-Toxin pore-associated 
      transmembrane Ca(2+) flux and PtdIns hydrolysis-related signaling with downstream 
      activation of protein kinase C and nuclear translocation of nuclear factor-kappaB 
      are suggested to represent important underlying mechanisms. Such reactivity of 
      the alveolar epithelial cells may be relevant for pathogenic sequelae in 
      staphylococcal lung disease.
FAU - Rose, Frank
AU  - Rose F
AD  - Department of Internal Medicine, Justus-Liebig University, Giessen D-35392, 
      Germany. Frank.Rose@innere.med.uni-giessen.de
FAU - Dahlem, Gabriele
AU  - Dahlem G
FAU - Guthmann, Bernd
AU  - Guthmann B
FAU - Grimminger, Friedrich
AU  - Grimminger F
FAU - Maus, Ulrich
AU  - Maus U
FAU - Hanze, Jorg
AU  - Hanze J
FAU - Duemmer, Nils
AU  - Duemmer N
FAU - Grandel, Ulrich
AU  - Grandel U
FAU - Seeger, Werner
AU  - Seeger W
FAU - Ghofrani, Hossein Ardeschir
AU  - Ghofrani HA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Bacterial Toxins)
RN  - 0 (Hemolysin Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Inositol Phosphates)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (staphylococcal alpha-toxin)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Bacterial Toxins/*pharmacology
MH  - Cell Line
MH  - Epithelial Cells/cytology/*drug effects/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Hemolysin Proteins/*pharmacology
MH  - Inflammation Mediators/*metabolism
MH  - Inositol Phosphates/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/genetics/metabolism
MH  - Male
MH  - Pneumonia/immunology/metabolism/microbiology
MH  - Pulmonary Alveoli/cytology/*immunology/microbiology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sepsis/immunology/metabolism/microbiology
MH  - Signal Transduction/*immunology
MH  - Staphylococcus aureus
EDAT- 2002/01/17 10:00
MHDA- 2002/03/08 10:01
CRDT- 2002/01/17 10:00
PHST- 2002/01/17 10:00 [pubmed]
PHST- 2002/03/08 10:01 [medline]
PHST- 2002/01/17 10:00 [entrez]
AID - 10.1152/ajplung.00156.2001 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282(2):L207-14. doi: 
      10.1152/ajplung.00156.2001.