Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis.
BACKGROUND
Transcription factor NF-kappaB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-kappaB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model.


METHODS
Using transgenic mice expressing photinus luciferase controlled by an NF-kappaB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-kappaB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid.


RESULTS
Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P < 0.05), and over the thorax at 60 and 72 h (P < 0.05). Luciferase assays showed significantly increased luciferase activity in both liver and lung tissue at 48 (liver = P < 0.005, lung = P < 0.05) and 60 h (liver = P < 0.05, lung = P < 0.05) compared to activity in uninjured controls. Total nucleated cell counts in BAL fluid were significantly increased at 72 h (P < 0.05) compared with controls.


CONCLUSIONS
In this model, NF-kappaB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.
Gray
Keith D
KD
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37208-3599, USA.
Simovic
Misho O
MO
Chapman
William C
WC
Blackwell
Timothy S
TS
Christman
John W
JW
Washington
M Kay
MK
Yull
Fiona E
FE
Jaffal
Nada
N
Jansen
E Duco
ED
Gautman
Shiva
S
Stain
Steven C
SC
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D005260:Female; D008099:Liver / Q000378:metabolism; D008156:Luciferases; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000150:complications / Q000378:metabolism*; D011014:Pneumonia / Q000209:etiology; D012016:Reference Values
D016328:NF-kappa B; D008156:Luciferases