Increased expression of cytokine induced neutrophil chemoattractant
(cinc) in septic rat liver.
Deutschman, Clifford S., Barbara A. Haber, Kenneth Andrejko, Drew E.
Cressman, Rachel Harrison, Eric Elenko, Rebecca Taub.
Department of Anesthesia, [grave]aDivision of Gastroenterology,
Children's Hospital of Philadelphia and the _Department of Genetics,
Howard Hughes Medical Institute, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania, 19104-4283
APStracts 3:0101R, 1996.
Hepatocellular dysfunction in sepsis may be neutrophil mediated.
Therefore, we tested the hypothesis that sepsis-induced neutrophil
accumulation is associated with increased expression of the chemokine
CINC . In Sprague-Dawley rats made septic using cecal ligation and
puncture we demonstrate a time-dependent increase in CINC mRNA which
returns to baseline by 48 hours. By in situ hybridization, this mRNA
is present in hepatocytes and nonparenchymal cells. CINC protein
levels in septic animals parallel mRNA levels and resolve by 48
hours. Since CINC expression is induced by cytokines including tumor
necrosis factor-a (TNF-a), we show, by immunohistochemistry, that
sepsis elevates intrahepatic TNF-[alpha] . Finally, since the CINC
promoter is transactivated by the transcription factor NF-kB, we
determined that hepatic NF-kB DNA binding increases dramatically,
peaking 16 hours following cecal ligation and puncture. Thus,
activated NF-kB may mediate CINC induction in sepsis. This
constellation of findings suggests a mechanism by which sepsis may
induce neutrophil accumulation in the liver and may have implications
regarding sepsis-induced hepatic dysfunction.
Received 4 October 1995; accepted in final form 3 March 1996.
APS Manuscript Number R623-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96