Lipopolysaccaride-mediated nf-kb activation in rat kupffer cells
can be induced independently of cd14 1.
Bellezzo, Joesph M., Robert S. Britton, Bruce R. Bacon, and Eben S.
Fox.
PEDIATRIC RESEARCH INSTITUTE, DEPARTMENT OF PEDIATRICS, DIVISION OF
GASTROENTEROLOGY AND HEPATOLOGY, DEPARTMENT OF INTERNAL MEDICINE,
SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE, ST. LOUIS, MO 63110
APStracts 2:0262G, 1995.
Lipopolysaccharide (LPS) activation of macrophages occurs after LPS
complexed with serum LPS-binding protein (LBP) binds CD14. Activation
of the transcription factor NF-kB is directly related to this event.
Since the role of CD14 in LPS signaling has not been evaluated in
Kupffer cells, the resident hepatic macrophage, the purpose of this
study was to characterize LPS-mediated NF-kB activation under CD14
-dependent (1% serum, as a source of LBP) and CD14-independent (serum
-free) conditions. Classic CD14-dependent signaling was seen in
peritoneal macrophages where serum potentiated NF-kB activation.
However, in Kupffer cells, NF-kB was activated by LPS under CD14
-independent conditions, and this response was not potentiated by
serum. The activation of NF-kB in Kupffer cells, by 1 ng/ml LPS,
reached a maximum within 60 minutes of stimulation. However,
peritoneal macrophage NF-kB activation occurred only in serum and
increased progressively through 240 minutes of stimulation. These
results suggest a novel mechanism of LPS-mediated activation in
Kupffer cells which may represent an adaptation to their role in
clearance and detoxification of gut-derived endotoxin.
Received 30 August 1995; accepted in final form 7 December 1995.
APS Manuscript Number G382-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95