Activation of STAT proteins in the lung of rats following resuscitation from hemorrhagic shock.
Hemorrhagic shock (HS) initiates a series of inflammatory processes, including the production of proinflammatory cytokines at critical sites such as the lung. We have previously shown that granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNA are produced in the lungs of rats subjected to resuscitated HS and that both the ischemic and reperfusion phases of resuscitated HS were required. G-CSF and IL-6 activate STAT (signal transducers and activators of transcription) proteins which may sustain the inflammatory response that follows resuscitation in HS. We tested the hypothesis that STAT proteins are activated in the lungs of rats subjected to resuscitated HS and examined the factors contributing to their activation including duration of shock and duration of resuscitation. Sprague-Dawley rats were subjected to compensated (66.1 +/- 1.1 min) or decompensated (157.3 +/- 2.3 min) HS (mean arterial pressure 40 mmHg) followed by resuscitation and sacrifice at 4 or 8 h. The amount of activated Stat3 was increased 2.3- to 7-fold compared with sham control animals in all four experimental groups of resuscitated HS. Levels of Stat3 activation increased with increase in duration of shock but did not demonstrate differences at the 4 or 8 h time point of killing. These results indicate that resuscitated HS results in the activation of the intracellular signaling cascade that includes that activation of STAT proteins driven by cytokines such as G-CSF and IL-6.
Department of Surgery, University of Pittsburgh School of Medicine, PA., USA.
C
C
Hierholzer
J C
JC
Kalff
T R
TR
Billiar
D J
DJ
Tweardy
D000209:Acute-Phase Proteins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D004586:Electrophoresis; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D050796:STAT3 Transcription Factor; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000628:therapy*; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*
D000209:Acute-Phase Proteins; D015415:Biomarkers; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators