Tumor necrosis factor-[alpha] inhibits lipid and lipoprotein
transport by caco-2 cells.
Mehran, M, Seidman E, Marchand R, Gurbindo C, and Levy E.
Departments of Nutrition and Pediatrics, Centre de Recherche,
H[circumflex]opital Sainte-Justine, Faculty of Medicine, University
of Montreal, Montreal, Quebec.
APStracts 2:0137G, 1995.
Cytokines, important mediators of inflammation, have been shown to
cause disturbances in circulating and hepatic lipid metabolism.
Although the intestine plays a major role in dietary fat transport
and largely contributes to plasma lipoproteins, the effects of
cytokines on intestinal lipid handling remain unknown. In the present
study, the modulation of lipid, apoprotein and lipoprotein synthesis
and secretion by tumor necrosis factor-alpha (TNF-[alpha]) was
investigated in Caco-2 cells. Highly differentiated and polarized
cells (20 days in culture) were incubated for 20 hours with
recombinant human TNF-[alpha] (100-500 ng/ml). No cytotoxic effect of
TNF-[alpha] cells was observed, as indicated by the determinations of
Caco-2 cell viability and monolayer transepithelialresistance.
Moreover, no differences in cell maturation (sucrase activity), nor
cell proliferation ([3H]-thymidine incorporation and cell cycle
analysis) were detected between treated and controls cultures.
Significant inhibition of lipid secretion by TNF-[alpha] was
observed, with the greatest reduction at 500 ng/ml. TNF-[alpha]
significantly decreased Caco-2 cell secretion of phospholipids (22%),
triglycerides (30%), and cholesteryl ester (37%). It also
significantly diminished the export of newly synthesized LDL (20%)
and HDL (13%), with a lesser effect on VLDL (3%). The lipid
composition of these lipoproteins was minimally affected. De novo
synthesis of apo A-I, apo B-100 and apo B-48 was also markedly
reduced by TNF-[alpha]. Sphingomyelinase activity was not increased
and cell content of sphingomyelin was not altered, suggesting that
inhibitory effects on lipid and apoprotein of TNF-[alpha] were not
mediated by the ceramide pathway. Our results indicate that TNF
-[alpha] may play a role in modulating intestinal lipid metabolism,
thus affecting circulating lipoproteins.
Received 27 December 1994; accepted in final form 24 June 1995.
APS Manuscript Number G502-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.