Luan Jie, Zhou Bingrong, Ding Hui, Qi Zhongtian
Department of Microbiology, State Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Acta Biochim Biophys Sin (Shanghai). 2007 Feb;39(2):96-100. doi: 10.1111/j.1745-7270.2007.00253.x.
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.
