DOI: 10.1126/science.8191285. Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors

Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors

10.1126/science.8191285

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Novogrodsky, A., Vanichkin, A., Patya, M., Gazit, A., Osherov, N., & Levitzki, A. (1994). Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors. Science, 264(5163), 1319â1322.

Authors 6

Abraham Novogrodsky (first)
Alexey Vanichkin (additional)
Miriam Patya (additional)
Aviv Gazit (additional)
Nir Osherov (additional)
Alexander Levitzki (additional)

References 40 Referenced 272

BEUTLER, B, TUMOR NECROSIS, CACHEXIA, SHOCK, AND INFLAMMATION - A COMMON MEDIATOR, ANNUAL REVIEW OF BIOCHEMISTRY 57: 505 (1988). (10.1146/annurev.bi.57.070188.002445) / ANNUAL REVIEW OF BIOCHEMISTRY (1988)
10.1126/science.3895437
BOHMER F unpublished data.
COYNE, D.W., EFFECT OF THE TYROSINE KINASE INHIBITOR, GENISTEIN, ON INTERLEUKIN-1 STIMULATED PGE2 PRODUCTION IN MESANGIAL CELLS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 173: 718 (1990). (10.1016/S0006-291X(05)80094-4) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1990)
DING, A.H., RELEASE OF REACTIVE NITROGEN INTERMEDIATES AND REACTIVE OXYGEN INTERMEDIATES FROM MOUSE PERITONEAL-MACROPHAGES - COMPARISON OF ACTIVATING CYTOKINES AND EVIDENCE FOR INDEPENDENT PRODUCTION, JOURNAL OF IMMUNOLOGY 141: 2407 (1988). (10.4049/jimmunol.141.7.2407) / JOURNAL OF IMMUNOLOGY (1988)
DONG, Z, JOURNAL OF EXPERIMENTAL MEDICINE 177: 1071 (1993). (10.1084/jem.177.4.1071) / JOURNAL OF EXPERIMENTAL MEDICINE (1993)
DONG, Z, ACTIVATION OF TUMORICIDAL PROPERTIES IN MACROPHAGES BY LIPOPOLYSACCHARIDE REQUIRES PROTEIN-TYROSINE KINASE-ACTIVITY, JOURNAL OF LEUKOCYTE BIOLOGY 53: 53 (1993). (10.1002/jlb.53.1.53) / JOURNAL OF LEUKOCYTE BIOLOGY (1993)
DONG, Z.Y., PROTEIN-TYROSINE KINASE INHIBITORS DECREASE INDUCTION OF NITRIC-OXIDE SYNTHASE ACTIVITY IN LIPOPOLYSACCHARIDE-RESPONSIVE AND LIPOPOLYSACCHARIDE-NONRESPONSIVE MURINE MACROPHAGES, JOURNAL OF IMMUNOLOGY 151: 2717 (1993). (10.4049/jimmunol.151.5.2717) / JOURNAL OF IMMUNOLOGY (1993)
EVERAERDT, B, 4 DIFFERENT INTERLEUKIN-1 SPECIES SENSITIZE TO THE LETHAL ACTION OF TUMOR NECROSIS FACTOR, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 163: 378 (1989). (10.1016/0006-291X(89)92146-3) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1989)
GADINA, M, PROTECTIVE EFFECT OF CHLORPROMAZINE ON ENDOTOXIN TOXICITY AND TNF PRODUCTION IN GLUCOCORTICOID-SENSITIVE AND GLUCOCORTICOID-RESISTANT MODELS OF ENDOTOXIC-SHOCK, JOURNAL OF EXPERIMENTAL MEDICINE 173: 1305 (1991). (10.1084/jem.173.6.1305) / JOURNAL OF EXPERIMENTAL MEDICINE (1991)
GAZIT, A, TYRPHOSTINS .1. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF PROTEIN TYROSINE KINASE INHIBITORS, JOURNAL OF MEDICINAL CHEMISTRY 32: 2344 (1989). (10.1021/jm00130a020) / JOURNAL OF MEDICINAL CHEMISTRY (1989)
GAZIT A unpublished data.
GEUNTER, C.A., J APPL PHYSIOL 26: 780 (1969). (10.1152/jappl.1969.26.6.780) / J APPL PHYSIOL (1969)
GLASER, K.B., REGULATION OF EICOSANOID BIOSYNTHESIS IN THE MACROPHAGE - INVOLVEMENT OF PROTEIN TYROSINE PHOSPHORYLATION AND MODULATION BY SELECTIVE PROTEIN TYROSINE KINASE INHIBITORS, BIOCHEMICAL PHARMACOLOGY 45: 711 (1993). (10.1016/0006-2952(93)90147-O) / BIOCHEMICAL PHARMACOLOGY (1993)
GREENMAN, R.L., A CONTROLLED CLINICAL-TRIAL OF E5 MURINE MONOCLONAL IGM ANTIBODY TO ENDOTOXIN IN THE TREATMENT OF GRAM-NEGATIVE SEPSIS, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION 266: 1097 (1991). (10.1001/jama.1991.03470080067031) / JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (1991)
GUY, G.R., INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR ACTIVATE COMMON MULTIPLE PROTEIN-KINASES IN HUMAN FIBROBLASTS, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 14343 (1991). (10.1016/S0021-9258(18)98690-4) / JOURNAL OF BIOLOGICAL CHEMISTRY (1991)
HOFFBARD, A.V., BLOOD 75: 88 (1990). (10.1182/blood.V75.1.88.88) / BLOOD (1990)
IWASAKI, T, HERBIMYCIN-A BLOCKS IL-1-INDUCED NF-KAPPA-B DNA-BINDING ACTIVITY IN LYMPHOID-CELL LINES, FEBS LETTERS 298: 240 (1992). (10.1016/0014-5793(92)80067-Q) / FEBS LETTERS (1992)
KILBOURN, R.G., OVERPRODUCTION OF NITRIC-OXIDE IN CYTOKINE-MEDIATED AND SEPTIC SHOCK, JOURNAL OF THE NATIONAL CANCER INSTITUTE 84: 827 (1992). (10.1093/jnci/84.11.827) / JOURNAL OF THE NATIONAL CANCER INSTITUTE (1992)
KILBOURN, R.G., NG-METHYL-L-ARGININE INHIBITS TUMOR NECROSIS FACTOR-INDUCED HYPOTENSION - IMPLICATIONS FOR THE INVOLVEMENT OF NITRIC-OXIDE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 3629 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
KOHMO, M, BIOCHEM J 267: 91 (1990). (10.1042/bj2670091) / BIOCHEM J (1990)
LEVITZKI, A, TYRPHOSTINS - TYROSINE KINASE BLOCKERS AS NOVEL ANTIPROLIFERATIVE AGENTS AND DISSECTORS OF SIGNAL TRANSDUCTION, FASEB JOURNAL 6: 3275 (1992). (10.1096/fasebj.6.14.1426765) / FASEB JOURNAL (1992)
Marczin, N., American Journal of Physiology-Heart and Circulatory Physiology 265: H1014 (1993). (10.1152/ajpheart.1993.265.3.H1014) / American Journal of Physiology-Heart and Circulatory Physiology (1993)
MUNOZ, E, INTERLEUKIN-1 INDUCES PROTEIN TYROSINE PHOSPHORYLATION IN T-CELLS, EUROPEAN JOURNAL OF IMMUNOLOGY 22: 1391 (1992). (10.1002/eji.1830220610) / EUROPEAN JOURNAL OF IMMUNOLOGY (1992)
OHLSSON, K, INTERLEUKIN-1 RECEPTOR ANTAGONIST REDUCES MORTALITY FROM ENDOTOXIN-SHOCK, NATURE 348: 550 (1990). (10.1038/348550a0) / NATURE (1990)
OKUSAWA, S, INTERLEUKIN-1 INDUCES A SHOCK-LIKE STATE IN RABBITS - SYNERGISM WITH TUMOR NECROSIS FACTOR AND THE EFFECT OF CYCLOOXYGENASE INHIBITION, JOURNAL OF CLINICAL INVESTIGATION 81: 1162 (1988). (10.1172/JCI113431) / JOURNAL OF CLINICAL INVESTIGATION (1988)
PARILLO, J.E., NEW ENGLAND JOURNAL OF MEDICINE 328: 1471 (1993). (10.1056/NEJM199305203282008) / NEW ENGLAND JOURNAL OF MEDICINE (1993)
PFEFFER, K, MICE DEFICIENT FOR THE 55KD TUMOR-NECROSIS-FACTOR RECEPTOR ARE RESISTANT TO ENDOTOXIC-SHOCK, YET SUCCUMB TO L-MONOCYTOGENES INFECTION, CELL 73: 457 (1993). (10.1016/0092-8674(93)90134-C) / CELL (1993)
Raetz, C. R., Annual Review of Biochemistry 59: 129 (1990). (10.1146/annurev.bi.59.070190.001021) / Annual Review of Biochemistry (1990)
REMICK, D.G., INVIVO DYNAMICS OF MURINE TUMOR NECROSIS FACTOR-ALPHA GENE-EXPRESSION - KINETICS OF DEXAMETHASONE-INDUCED SUPPRESSION, LABORATORY INVESTIGATION 60: 766 (1989). / LABORATORY INVESTIGATION (1989)
ROTHE, J, MICE LACKING THE TUMOR-NECROSIS-FACTOR RECEPTOR-1 ARE RESISTANT TO TNF-MEDIATED TOXICITY BUT HIGHLY SUSCEPTIBLE TO INFECTION BY LISTERIA-MONOCYTOGENES, NATURE 364: 798 (1993). (10.1038/364798a0) / NATURE (1993)
STEFANOVA, I, LIPOPOLYSACCHARIDE INDUCES ACTIVATION OF CD14-ASSOCIATED PROTEIN-TYROSINE KINASE P53/56LYN, JOURNAL OF BIOLOGICAL CHEMISTRY 268: 20725 (1993). (10.1016/S0021-9258(19)36840-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1993)
TSUNAWAKI, S, ENZYMATIC BASIS OF MACROPHAGE ACTIVATION - KINETIC-ANALYSIS OF SUPEROXIDE PRODUCTION IN LYSATES OF RESIDENT AND ACTIVATED MOUSE PERITONEAL-MACROPHAGES AND GRANULOCYTES, JOURNAL OF BIOLOGICAL CHEMISTRY 259: 4305 (1984). (10.1016/S0021-9258(17)43046-8) / JOURNAL OF BIOLOGICAL CHEMISTRY (1984)
VICTOR, I, J BIOL CHEM 268: 18994 (1993). (10.1016/S0021-9258(17)46725-1) / J BIOL CHEM (1993)
WALLACH, D, SENSITIZATION AND DESENSITIZATION TO LETHAL EFFECTS OF TUMOR NECROSIS FACTOR AND IL-1, JOURNAL OF IMMUNOLOGY 140: 2994 (1988). (10.4049/jimmunol.140.9.2994) / JOURNAL OF IMMUNOLOGY (1988)
WEINSTEIN, S.L., BACTERIAL LIPOPOLYSACCHARIDE INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES IN MACROPHAGES, JOURNAL OF BIOLOGICAL CHEMISTRY 267: 14955 (1992). (10.1016/S0021-9258(18)42133-3) / JOURNAL OF BIOLOGICAL CHEMISTRY (1992)
WEINSTEIN, S.L., BACTERIAL LIPOPOLYSACCHARIDE STIMULATES PROTEIN TYROSINE PHOSPHORYLATION IN MACROPHAGES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 4148 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
10.1126/science.3263702
ZANG, X, JOURNAL OF EXPERIMENTAL MEDICINE 177: 511 (1993). (10.1084/jem.177.2.511) / JOURNAL OF EXPERIMENTAL MEDICINE (1993)
ZIEGLER, E.J., TREATMENT OF GRAM-NEGATIVE BACTEREMIA AND SHOCK WITH HUMAN ANTISERUM TO A MUTANT ESCHERICHIA-COLI, NEW ENGLAND JOURNAL OF MEDICINE 307: 1225 (1982). (10.1056/NEJM198211113072001) / NEW ENGLAND JOURNAL OF MEDICINE (1982)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited	1 year, 7 months ago (Jan. 15, 2024, 12:34 a.m.)
Indexed	2 days, 7 hours ago (Sept. 3, 2025, 6:36 a.m.)
Issued	31 years, 3 months ago (May 27, 1994)
Published	31 years, 3 months ago (May 27, 1994)
Published Print	31 years, 3 months ago (May 27, 1994)

Funders 0

None

BibTeX

@article{Novogrodsky_1994, title={Prevention of Lipopolysaccharide-Induced Lethal Toxicity by Tyrosine Kinase Inhibitors}, volume={264}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8191285}, DOI={10.1126/science.8191285}, number={5163}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Novogrodsky, Abraham and Vanichkin, Alexey and Patya, Miriam and Gazit, Aviv and Osherov, Nir and Levitzki, Alexander}, year={1994}, month=may, pages={1319–1322} }

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      "DOI": "10.1096/fasebj.6.14.1426765",
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      "journal-title": "NEW ENGLAND JOURNAL OF MEDICINE"
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      "DOI": "10.1016/0092-8674(93)90134-C",
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      "DOI": "10.1146/annurev.bi.59.070190.001021",
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      "DOI": "10.1038/364798a0",
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      "DOI": "10.4049/jimmunol.140.9.2994",
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