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Science 27 May 1994:
Vol. 264. no. 5163, pp. 1319 - 1322
DOI: 10.1126/science.8191285
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Articles

Science, Vol 264, Issue 5163, 1319-1322
Copyright © 1994 by American Association for the Advancement of Science

articles

Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors

A Novogrodsky, A Vanichkin, M Patya, A Gazit, N Osherov, and A Levitzki

Felsenstein Medical Research Center, Petach Tikva, Israel.

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 alpha (TNF-alpha) and nitric oxide in macrophages as well as LPS-induced production of TNF-alpha in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42MAPK protein substrate in the murine macrophage.


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D. Bani, P. Failli, M. G. Bello, C. Thiemermann, T. B. Sacchi, M. Bigazzi, and E. Masini (1998)
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Involvement of C-Abl Tyrosine Kinase in Lipopolysaccharide- Induced Macrophage Activation.
Q. Le, R. Daniel, S.-W. Chung, A. D. Kang, T. K. Eisenstein, B. M. Sultzer, H. Simpkins, and P. M. C. Wong (1998)
J. Immunol. 160, 3330-3336
   Abstract »    Full Text »    PDF »
Protein tyrosine phosphorylation mediates TNF-induced endothelial-neutrophil adhesion in vitro.
S. A. Kelly, P. J. Goldschmidt-Clermont, E. E. Milliken, T. Arai, E. H. Smith, and G. B. Bulkley (1998)
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   Abstract »    Full Text »    PDF »
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Arch Surg 131, 1273-1279
   Abstract »    PDF »
Protein-tyrosine Kinase Activation Is Required for Lipopolysaccharide Induction of Interleukin 1beta and NFkappa B Activation, but Not NFkappa B Nuclear Translocation.
B. K. Yoza, J. Y.Q. Hu, and C. E. McCall (1996)
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Lactosylceramide Stimulates Ras-GTP Loading, Kinases (MEK, Raf), p44 Mitogen-activated Protein Kinase, and c-fos Expression in Human Aortic Smooth Muscle Cells.
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S.A. Barber, C.A. Salkowski, M.J. Fultz, P-Y. Perera, R. McNally, and S.N. Vogel (1996)
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R. Silverstein, W.M. Johnson, S.E. Bucklin, and D.C. Johnson (1996)
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Regulation of Cytokine-inducible Nitric Oxide Synthase in Cardiac Myocytes and Microvascular Endothelial Cells.
K. Singh, J.-L. Balligand, T. A. Fischer, T. W. Smith, and R. A. Kelly (1996)
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L. Li, S. Cousart, J. Hu, and C. E. McCall (2000)
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ATP-stimulated Release of Interleukin (IL)-1beta and IL-18 Requires Priming by Lipopolysaccharide and Is Independent of Caspase-1 Cleavage.
V. B. Mehta, J. Hart, and M. D. Wewers (2001)
J. Biol. Chem. 276, 3820-3826
   Abstract »    Full Text »    PDF »
Mitogen-activated Protein Kinases Mediate Activator Protein-1-dependent Human Inducible Nitric-oxide Synthase Promoter Activation.
A. S. Kristof, J. Marks-Konczalik, and J. Moss (2001)
J. Biol. Chem. 276, 8445-8452
   Abstract »    Full Text »    PDF »


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