Lipopolysaccharide signal transduction, regulation of tumor necrosis factor biosynthesis, and signaling by tumor necrosis factor itself

B. Beutler, V. Kruys

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

In recent years, the chain of events that connects introduction of bacterial endotoxin (lipopolysaccharide: LPS) into a mammalian host, and the syndrome of organ damage and vascular collapse that ensues, have come into sharper focus. Several of the molecules that engage LPS, and a rough outline of the signaling cascade that leads to cytokine release from mononuclear cells, have been elucidated. The principal cytokines that mediate the untoward effects of LPS have also been identified. The most important of these is tumor necrosis factor (TNF), which elicits biologic responses from virtually every type of cell to which it binds. Two distinct receptors transduce the TNF signal. Mechanisms of TNF receptor action are becoming increasing clear, and there is reason to hope that, through intervention at many distinct levels, the devastating effects of LPS might be attenuated or averted.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume25
Issue numberSUPPL. 2
DOIs
StatePublished - 1995

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Tumor Necrosis Factor Receptors
Lipopolysaccharides
Signal Transduction
Tumor Necrosis Factor-alpha
Cytokines
Endotoxins
Blood Vessels

Keywords

  • hypotension
  • lipopolysaccharide
  • septic shock
  • tumor necrosis factor

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

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abstract = "In recent years, the chain of events that connects introduction of bacterial endotoxin (lipopolysaccharide: LPS) into a mammalian host, and the syndrome of organ damage and vascular collapse that ensues, have come into sharper focus. Several of the molecules that engage LPS, and a rough outline of the signaling cascade that leads to cytokine release from mononuclear cells, have been elucidated. The principal cytokines that mediate the untoward effects of LPS have also been identified. The most important of these is tumor necrosis factor (TNF), which elicits biologic responses from virtually every type of cell to which it binds. Two distinct receptors transduce the TNF signal. Mechanisms of TNF receptor action are becoming increasing clear, and there is reason to hope that, through intervention at many distinct levels, the devastating effects of LPS might be attenuated or averted.",
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AB - In recent years, the chain of events that connects introduction of bacterial endotoxin (lipopolysaccharide: LPS) into a mammalian host, and the syndrome of organ damage and vascular collapse that ensues, have come into sharper focus. Several of the molecules that engage LPS, and a rough outline of the signaling cascade that leads to cytokine release from mononuclear cells, have been elucidated. The principal cytokines that mediate the untoward effects of LPS have also been identified. The most important of these is tumor necrosis factor (TNF), which elicits biologic responses from virtually every type of cell to which it binds. Two distinct receptors transduce the TNF signal. Mechanisms of TNF receptor action are becoming increasing clear, and there is reason to hope that, through intervention at many distinct levels, the devastating effects of LPS might be attenuated or averted.

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