Abstract
Lipopolysaccharide and D-galactosamine induced lethality and apoptotic liver injury is dependent on endogenously produced tumor necrosis factor (TNF)-α. The present study was undertaken to determine whether membrane- associated or secreted TNF-α signaling through the p55 or p75 receptor was responsible for survival and hepatic injury after lipopolysaccharide administration in D-galactosamine-sensitized mice. Transgenic mice expressing null forms of TNF-α, the p55 and p75 receptor, and mice expressing only a cell-associated form of TNF-α were challenged with 8 mg D-galactosamine and 100 ng lipopolysaccharide. Mortality and apoptotic liver injury were only seen in wild-type and p75 knockout mice. p75 Knockout mice had significantly higher concentrations of plasma TNF-α than any other experimental group (P ≤ 0.05) and tended to have the highest mortality and liver injury. In contrast, p55 and TNF-α knockout mice and animals expressing only a cell- associated form of TNF-α exhibited no mortality or liver injury. We conclude that survival and apoptotic liver injury in response to lipopolysaccharide and D-galactosamine are dependent exclusively on secreted TNF-α signaling through the p55 receptor.
Original language | English (US) |
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Pages (from-to) | R1202-R1209 |
Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
Volume | 278 |
Issue number | 5 47-5 |
DOIs | |
State | Published - 2000 |
Keywords
- Apoptosis
- Hepatitis
- Septic shock
ASJC Scopus subject areas
- Physiology
- Physiology (medical)