Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2005; 11(22): 3398-3404
Published online Jun 14, 2005. doi: 10.3748/wjg.v11.i22.3398
Lethal effect and apoptotic DNA fragmentation in response of D-GalN-treated mice to bacterial LPS can be suppressed by pre-exposure to minute amount of bacterial LPS: Dual role of TNF receptor 1
Bing-Rong Zhou, Marina Gumenscheimer, Marina A. Freudenberg, Chris Galanos
Bing-Rong Zhou, Department of Microbiology, Second Military Medical University, Shanghai 200433, China
Marina Gumenscheimer, Marina A. Freudenberg, Chris Galanos, Max-Planck-Institut für Immunbiologie Stübeweg 51 D-79108 Freiburg in Br. Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Chris Galanos, Max-Planck-Institut für Immunbiologie Stübeweg 51 D-79108 Freiburg in Br. Germany. galanos@immunbio.mpg.de
Telephone: +49-761-5108400 Fax: +49-761-5108403
Received: March 15, 2004
Revised: March 16, 2004
Accepted: April 29, 2004
Published online: June 14, 2005
Abstract

AIM: To investigate whether induction of tolerance of mice to lipopolysaccharide (LPS) was able to inhibit apoptotic reaction in terms of characteristic DNA fragmentation and protect mice from lethal effect.

METHODS: Experimental groups of mice were pretreated with non-lethal amount of LPS (0.05 μg). Both control and experimental groups simultaneously were challenged with LPS plus D-GalN for 6-7 h. The evaluations of both DNA fragmentations from the livers and the protection efficacy against lethality to mice through induction of tolerance to LPS were conducted.

RESULTS: In the naive mice challenge with LPS plus D-GalN resulted in complete death in 24 h, whereas a characteristic apoptotic DNA fragmentation was exclusively seen in the livers of mice receiving LPS in combination with D-GalN. The mortality in the affected mice was closely correlated to the onset of DNA fragmentation. By contrast, in the mice pre-exposed to LPS, both lethal effect and apoptotic DNA fragmentation were suppressed when challenged with LPS/D-GalN. In addition to LPS, the induction of mouse tolerance to TNF also enabled mice to cross-react against death and apoptotic DNA fragmentation when challenged with TNF and/or LPS in the presence of D-GalN. Moreover, this protection effect by LPS could last up to 24 h. TNFR1 rather than TNFR2 played a dual role in signaling pathway of either induction of tolerance to LPS for the protection of mice from mortality or inducing morbidity leading to the death of mice.

CONCLUSION: The mortality of D-GalN-treated mice in response to LPS was exceedingly correlated to the onset of apoptosis in the liver, which can be effectively suppressed by brief exposure of mice to a minute amount of LPS. The induced tolerance status was mediated not only by LPS but also by TNF. The developed tolerance to either LPS or TNF can be reciprocally cross-reacted between LPS and TNF challenges, whereas the signaling of induction of tolerance and promotion of apoptosis was through TNFR1, rather than TNFR2.

Keywords: LPS tolerance; DNA fragmentation; Apoptosis; TNF receptor