LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor

Monika Nowak, Gregory C. Gaines, Jason Rosenberg, Rebecca Minter, Frances Bahjat, John Rectenwald, Sally L D Mackay, Carl K. Edwards, Lyle L. Moldawer

Research output: Contribution to journalArticle

148 Citations (Scopus)

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 languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume278
Issue number5 47-5
StatePublished - 2000
Externally publishedYes

Fingerprint

Galactosamine
Tumor Necrosis Factor Receptors
Tumor Necrosis Factor-alpha
Liver
Wounds and Injuries
Lipopolysaccharides
Knockout Mice
Mortality
Transgenic Mice
Membranes

Keywords

  • Apoptosis
  • Hepatitis
  • Septic shock

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor. / Nowak, Monika; Gaines, Gregory C.; Rosenberg, Jason; Minter, Rebecca; Bahjat, Frances; Rectenwald, John; Mackay, Sally L D; Edwards, Carl K.; Moldawer, Lyle L.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 278, No. 5 47-5, 2000.

Research output: Contribution to journalArticle

Nowak, M, Gaines, GC, Rosenberg, J, Minter, R, Bahjat, F, Rectenwald, J, Mackay, SLD, Edwards, CK & Moldawer, LL 2000, 'LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 278, no. 5 47-5.
Nowak, Monika ; Gaines, Gregory C. ; Rosenberg, Jason ; Minter, Rebecca ; Bahjat, Frances ; Rectenwald, John ; Mackay, Sally L D ; Edwards, Carl K. ; Moldawer, Lyle L. / LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2000 ; Vol. 278, No. 5 47-5.
@article{20427212158646f1ae61c9cbcca4db3f,
title = "LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor",
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.",
keywords = "Apoptosis, Hepatitis, Septic shock",
author = "Monika Nowak and Gaines, {Gregory C.} and Jason Rosenberg and Rebecca Minter and Frances Bahjat and John Rectenwald and Mackay, {Sally L D} and Edwards, {Carl K.} and Moldawer, {Lyle L.}",
year = "2000",
language = "English (US)",
volume = "278",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5 47-5",

}

TY - JOUR

T1 - LPS-induced liver injury in D-galactosamine-sensitized mice requires secreted TNF-α and the TNF-p55 receptor

AU - Nowak, Monika

AU - Gaines, Gregory C.

AU - Rosenberg, Jason

AU - Minter, Rebecca

AU - Bahjat, Frances

AU - Rectenwald, John

AU - Mackay, Sally L D

AU - Edwards, Carl K.

AU - Moldawer, Lyle L.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Hepatitis

KW - Septic shock

UR - http://www.scopus.com/inward/record.url?scp=0034048115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034048115&partnerID=8YFLogxK

M3 - Article

C2 - 10801288

AN - SCOPUS:0034048115

VL - 278

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5 47-5

ER -