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rdf:type |
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lifeskim:mentions |
umls-concept:C0015744,
umls-concept:C0017262,
umls-concept:C0185117,
umls-concept:C0287531,
umls-concept:C1333257,
umls-concept:C1366876,
umls-concept:C1705047,
umls-concept:C1833235,
umls-concept:C2587213,
umls-concept:C2911684,
umls-concept:C2911691
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pubmed:issue |
2
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pubmed:dateCreated |
2007-1-1
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pubmed:abstractText |
Mitogen-activated protein (MAP) kinases play a critical role in innate immune responses to microbial infection through eliciting the biosynthesis of proinflammatory cytokines. MAP phosphatases (MKP)-1 is an archetypical member of the dual-specificity phosphatase family that deactivates MAP kinases. Induction of MKP-1 has been implicated in attenuating the lipopolysaccharide (LPS) and Peptidoglycan (PGN) responses, but how the expression of the MKP-1 is regulated is still not fully understood. Here, we show that inhibition of p38 MAP kinase by specific inhibitor SB 203580 or RNA interference (RNAi) markedly reduced the expression of MKP-1 in LPS or PGN-treated macrophages, which is correlated with prolonged activation of p38 and JNK. Depletion of MAPKAP kinase 2 (MK2), a downstream substrate of p38, by RNAi also inhibited the expression of MKP-1. The mRNA level of MKP-1 is not affected by inhibition of p38, but the expression of MKP-1 is inhibited by treatment of cycloheximide. Thus, p38 MAPK plays a critical role in mediating expression of MKP-1 at a post-transcriptional level. Furthermore, inhibition of p38 by SB 203580 prevented the expression of MKP-1 in LPS-tolerized macrophages, restored the activation of MAP kinases after LPS restimulation. These results indicate a critical role of p38-MK2-dependent induction of MKP-1 in innate immune responses.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Dusp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP-kinase-activated kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidoglycan,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0898-6568
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
393-400
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16978838-Animals,
pubmed-meshheading:16978838-Cell Cycle Proteins,
pubmed-meshheading:16978838-Cells, Cultured,
pubmed-meshheading:16978838-Drug Interactions,
pubmed-meshheading:16978838-Drug Tolerance,
pubmed-meshheading:16978838-Dual Specificity Phosphatase 1,
pubmed-meshheading:16978838-Enzyme Activation,
pubmed-meshheading:16978838-Feedback, Physiological,
pubmed-meshheading:16978838-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16978838-Imidazoles,
pubmed-meshheading:16978838-Immediate-Early Proteins,
pubmed-meshheading:16978838-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16978838-Lipopolysaccharides,
pubmed-meshheading:16978838-MAP Kinase Kinase 4,
pubmed-meshheading:16978838-Macrophages,
pubmed-meshheading:16978838-Male,
pubmed-meshheading:16978838-Mice,
pubmed-meshheading:16978838-Mice, Inbred BALB C,
pubmed-meshheading:16978838-Models, Biological,
pubmed-meshheading:16978838-Peptidoglycan,
pubmed-meshheading:16978838-Phosphoprotein Phosphatases,
pubmed-meshheading:16978838-Protein Biosynthesis,
pubmed-meshheading:16978838-Protein Kinases,
pubmed-meshheading:16978838-Protein Phosphatase 1,
pubmed-meshheading:16978838-Protein Tyrosine Phosphatases,
pubmed-meshheading:16978838-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16978838-Pyridines,
pubmed-meshheading:16978838-RNA Interference,
pubmed-meshheading:16978838-Signal Transduction,
pubmed-meshheading:16978838-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Feedback control of MKP-1 expression by p38.
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pubmed:affiliation |
Signal Transduction Lab of Institute of Health Sciences, Shanghai Institutes for Biological Sciences [corrected] Chinese Academy of Sciences & [corrected] Shanghai Jiao-Tong University School of Medicine, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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