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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0023273,
umls-concept:C0024432,
umls-concept:C0037083,
umls-concept:C0087140,
umls-concept:C0132555,
umls-concept:C0185117,
umls-concept:C0599946,
umls-concept:C0752312,
umls-concept:C1710082,
umls-concept:C1879547,
umls-concept:C2261672,
umls-concept:C2911684
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pubmed:issue |
8
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pubmed:dateCreated |
1999-8-12
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pubmed:abstractText |
Intracellular protozoan parasites of the genus Leishmania antagonize host defense mechanisms by interfering with cell signaling in macrophages. In this report, the impact of Leishmania donovani on mitogen-activated protein (MAP) kinases and nitric oxide synthase (NOS) expression in the macrophage cell line RAW 264 was investigated. Overnight infection of cells with leishmania led to a significant decrease in phorbol-12-myristate-13-acetate (PMA)-stimulated MAP kinase activity and inhibited PMA-induced phosphorylation of the MAP kinase substrate and transcription factor Elk-1. Simultaneously, leishmania infection markedly attenuated the induction of c-FOS and inducible nitric oxide synthase (iNOS) expression in response to PMA and gamma interferon (IFN-gamma), respectively. These effects correlated with decreased phosphorylation of p44 and p42 MAP kinases on tyrosine residues. Consistent with the latter finding, lysates prepared from leishmania-infected cells contained an activity that dephosphorylated MAP kinase in vitro, suggesting the possibility of a phosphatase acting in vivo. Attenuation of both MAP kinase activity and c-FOS and iNOS expression was reversed by treatment of macrophages with sodium orthovanadate prior to infection. It was also found that the specific activity of the Src homology 2 domain containing tyrosine phosphatase (SHP-1) toward MAP kinase was markedly increased in leishmania-infected cells. These findings indicate that infection with L. donovani attenuates MAP kinase signaling and c-FOS and iNOS expression in macrophages by activating cellular phosphotyrosine phosphatases. This may represent a novel mechanism of macrophage deactivation during intracellular infection.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1314226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1321146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1322499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1323839,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1323888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1444269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1711326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1737935,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1802411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1849075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-1943774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-2139661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-2967971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7504064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7512963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7518460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7539113,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7591091,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7598304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7683430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7705404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7834742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-7916951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-8386592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-8392180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-8452678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-8482844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-8701794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10417174-9417127
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Elk1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/ets-Domain Protein Elk-1
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0019-9567
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4055-63
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10417174-Animals,
pubmed-meshheading:10417174-Mice,
pubmed-meshheading:10417174-Tyrosine,
pubmed-meshheading:10417174-Phosphorylation,
pubmed-meshheading:10417174-Macrophages,
pubmed-meshheading:10417174-Cell Line,
pubmed-meshheading:10417174-Enzyme Activation,
pubmed-meshheading:10417174-Leishmania donovani,
pubmed-meshheading:10417174-DNA-Binding Proteins,
pubmed-meshheading:10417174-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10417174-Transcription Factors,
pubmed-meshheading:10417174-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10417174-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10417174-Protein Tyrosine Phosphatases,
pubmed-meshheading:10417174-Proto-Oncogene Proteins,
pubmed-meshheading:10417174-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:10417174-ets-Domain Protein Elk-1,
pubmed-meshheading:10417174-Nitric Oxide Synthase,
pubmed-meshheading:10417174-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:10417174-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:10417174-Nitric Oxide Synthase Type II
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