TY - JOUR
T1 - Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors
AU - Novogrodsky, Abraham
AU - Vanichkin, Alexey
AU - Patya, Miriam
AU - Gazit, Aviv
AU - Osherov, Nir
AU - Levitzki, Alexander
PY - 1994/5/27
Y1 - 1994/5/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0028343059&partnerID=8YFLogxK
U2 - 10.1126/science.8191285
DO - 10.1126/science.8191285
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C2 - 8191285
AN - SCOPUS:0028343059
SN - 0036-8075
VL - 264
SP - 1319
EP - 1322
JO - Science
JF - Science
IS - 5163
ER -