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rdf:type |
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lifeskim:mentions |
umls-concept:C0014264,
umls-concept:C0024432,
umls-concept:C0033634,
umls-concept:C0109317,
umls-concept:C0439851,
umls-concept:C0591833,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1552596,
umls-concept:C1555029,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1879547,
umls-concept:C1947931,
umls-concept:C1948023
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pubmed:issue |
2
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pubmed:dateCreated |
2000-11-21
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pubmed:abstractText |
Lipopolysaccharide (LPSp) pretreatment inhibits TNF secretion in endotoxin-tolerant macrophages via alterations in signal transduction pathways of LPS activation (LPSa). Protein kinase C inhibitors prevent TNF release in response to LPSa and direct protein kinase C activation with phorbol myristate acetate (PMA) restores TNF secretion after LPSp. In the current experiments the effect of protein kinase C modulation on LPSa-stimulated ERK 1/2 activation was investigated. Murine macrophage TNF production was determined after stimulation with 100 ng/mL of LPSa, +/- 24 h pretreatment with 10 ng/mL of LPSp. Direct protein kinase C activators (PMA or indolactam) or inhibitors (H7 or bisindolylmaleimide) were added 1 h before LPSa. Diphosphorylated ERK 1/2 was assayed after LPSa stimulation by Western blot. LPS tolerance after LPSp was characterized by inhibition of LPSa-stimulated TNF and accompanied by impaired ERK 1/2 activation by LPSa. Protein kinase C activation with PMA or indolactam restored ERK 1/2 activation and TNF secretion. Inhibition of protein kinase C with H7 or bisindolylmaleimide prevented TNF secretion and ERK 1/2 activation by LPSa. These findings suggest that both ERK 1/2 and protein kinase C are required for TNF production in nontolerant macrophages and that LPS tolerance may be associated with an inability to phosphorylate ERK 1/2.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide,
http://linkedlifedata.com/resource/pubmed/chemical/indolactam V
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1073-2322
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-75
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10947162-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:10947162-Animals,
pubmed-meshheading:10947162-Drug Tolerance,
pubmed-meshheading:10947162-Enzyme Activation,
pubmed-meshheading:10947162-Enzyme Inhibitors,
pubmed-meshheading:10947162-Flavonoids,
pubmed-meshheading:10947162-Gene Expression Regulation,
pubmed-meshheading:10947162-Indoles,
pubmed-meshheading:10947162-Lactams,
pubmed-meshheading:10947162-Lipopolysaccharides,
pubmed-meshheading:10947162-MAP Kinase Signaling System,
pubmed-meshheading:10947162-Macrophages, Peritoneal,
pubmed-meshheading:10947162-Male,
pubmed-meshheading:10947162-Maleimides,
pubmed-meshheading:10947162-Mice,
pubmed-meshheading:10947162-Mice, Inbred BALB C,
pubmed-meshheading:10947162-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:10947162-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:10947162-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10947162-Phosphorylation,
pubmed-meshheading:10947162-Protein Kinase C,
pubmed-meshheading:10947162-Protein Processing, Post-Translational,
pubmed-meshheading:10947162-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10947162-Tumor Necrosis Factor-alpha
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pubmed:year |
2000
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pubmed:articleTitle |
Defective lipopolysaccharide-dependent ERK 1/2 activation in endotoxin tolerant murine macrophages is reversed by direct protein kinase C stimulation.
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pubmed:affiliation |
Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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