Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors
- 27 May 1994
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 264 (5163) , 1319-1322
- https://doi.org/10.1126/science.8191285
Abstract
Septic shock results from excessive stimulation of the host immune system, especially macrophages, by lipopolysaccharide (LPS), or endotoxin, which resides on the outer membrane of bacteria. Protein tyrosine kinase inhibitors of the tyrphostin AG 126 family protect mice against LPS-induced lethal toxicity. The protection correlates with the ability of these agents to block LPS-induced production of tumor necrosis factor α (TNF-α) and nitric oxide in macrophages as well as LPS-induced production of TNF-α in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42 MAPK protein substrate in the murine macrophage.Keywords
This publication has 35 references indexed in Scilit:
- Tyrosine phosphorylation of mitogen-activated protein kinases is necessary for activation of murine macrophages by natural and synthetic bacterial products.The Journal of Experimental Medicine, 1993
- Lipopolysaccharide-induced selective priming effects on tumor necrosis factor alpha and nitric oxide production in mouse peritoneal macrophages.The Journal of Experimental Medicine, 1993
- Interleukin‐1 induces protein tyrosine phosphorylation in T cellsEuropean Journal of Immunology, 1992
- Herbimycin A blocks IL‐1‐induced NF‐κB DNA‐binding activity in lymphoid cell linesFEBS Letters, 1992
- Interleukin-1 receptor antagonist reduces mortality from endotoxin shockNature, 1990
- Effect of the tyrosine kinase inhibitor, genistein, on interleukin-1 stimulated PGE2 production in mesangial cellsBiochemical and Biophysical Research Communications, 1990
- BIOCHEMISTRY OF ENDOTOXINSAnnual Review of Biochemistry, 1990
- Four different interleukin-1 species sensitize to the lethal action of Tumour Necrosis FactorBiochemical and Biophysical Research Communications, 1989
- Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.Journal of Clinical Investigation, 1988
- Treatment of Gram-Negative Bacteremia and Shock with Human Antiserum to a MutantEscherichia coliNew England Journal of Medicine, 1982