Tolerance of mice to lipopolysaccharide is correlated with inhibition of caspase-3-mediated apoptosis in mouse liver cells.
Bacterial endotoxin lipopolysaccharide (LPS) often results in multiple organ failure. However, pre-exposure of mice to a sublethal dose of LPS renders the animal tolerant to a lethal dose of LPS. This study was designed to determine whether pre-exposure of a small dose of LPS was able to suppress apoptosis in mice when challenged with LPS in combination with D-galactosamine, and to investigate the expression changes of the apoptosis-associated molecules. The results showed that a characteristic apoptotic DNA fragmentation existed in mouse livers of the LPS-naive group, but not in control groups; and the mice of the LPS-naive group were all dead after 2 d. However, in the LPS-tolerance groups, both the lethal rate and apoptotic DNA fragmentation were suppressed after the mice were challenged with LPS/D-galactosamine, and the protection against the lethality and apoptotic reaction could be maintained for up to 7 d. In this period, significantly lower levels of caspase-3 and its mRNA appeared in LPS-tolerant groups compared to those of the LPS-naive group (P<0.05), and the caspase-3 activities gradually recovered as the observation was prolonged. Our findings suggest that LPS tolerance could suppress apoptosis in mouse liver cells, and the expression and activity of caspase-3 could be down-regulated.
Luan
Jie
J
Department of Microbiology, State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Zhou
Bingrong
B
Ding
Hui
H
Qi
Zhongtian
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D004247:DNA / Q000302:isolation & purification; D053938:DNA Fragmentation; D004361:Drug Tolerance; D005260:Female; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D061945:Caspase Inhibitors; D008070:Lipopolysaccharides; D004247:DNA