Chylomicron-bound LPS selectively inhibits the hepatocellular response to proinflammatory cytokines.
OBJECTIVE
Pretreatment of rodent hepatocytes with chylomicron-bound lipopolysaccharide (CM-LPS) renders these cells unresponsive to subsequent stimulation by proinflammatory cytokines. We sought to test the selectivity of this response.


METHODS
Cellular responses to hypoxia, oxidative stress, apoptosis, and heat-shock response, and thermotolerance induced in CM-LPS pretreated hepatocytes were compared with responses in non-pretreated cells.


RESULTS
CM-LPS inhibited the hepatocellular response to proinflammatory cytokines without affecting the response to the other cellular stressors. It did not affect the response to oxidative stress, as measured by mitochondrial activity after hydrogen peroxide was added, or protein induction before or after stimulation with cobalt chloride. Also, induction of heat shock proteins did not differ between the CM-LPS pretreated cells and non-pretreated cells. CM-LPS did not interfere with the adoption of the thermotolerant phenotype, as shown by similar mitochondrial activity between pretreated and non-pretreated cells. Although stimulation with tumor necrosis factor-alpha and actinomycin D increased activity of the apoptotic enzymes, there were no differences between cells pretreated with CM-LPS and non-pretreated hepatocytes.


CONCLUSIONS
When the response to proinflammatory cytokines is inhibited, hepatocellular responses to hypoxia, oxidative stress, heat shock, and apoptosis remain intact after pretreatment with CM-LPS. CM-LPS may have a specific anti-inflammatory effect on hepatocytes.
Kasravi
Behzad
B
University of California, San Francisco, Surgical Research Laboratory at San Francisco General Hospital, San Francisco, California 94110-3518, USA.
Lee
Diana H
DH
Lee
Jean W
JW
Dada
Stephen
S
Harris
Hobart W
HW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D002914:Chylomicrons / Q000494:pharmacology*; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002914:Chylomicrons; D006360:Heat-Shock Proteins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma
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