Source:http://linkedlifedata.com/resource/pubmed/id/19029199
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-4-1
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| pubmed:abstractText |
Neuropeptide modulation of immune cell function is an important mechanism of neuro-immune intersystem crosstalk. Substance P (SP) is one such key neuropeptide involved. In this study, we investigated the yet unexplored cellular mechanisms of SP-mediated inflammatory responses in macrophages using a mouse macrophage-like cell line RAW 264.7 and isolated peritoneal macrophages. We found that the conventional PKCalpha and novel PKCdelta and epsilon were selectively activated by SP via its primary neurokinin-1 receptor (NK-1R) on the cells. Activation of these PKC isoforms mediated the activation of downstream extracellular signal-regulated kinase-1/2 (ERK1/2) and the transcription factor NF-kappaB, which drove the transcription of inducible chemokines in macrophages. Additionally, phosphoinositide 3-kinase (PI3K)-Akt was also activated by SP/NK-1R in macrophages. Inhibition of PI3K-Akt pathway attenuated ERK1/2 and NF-kappaB activation, suggesting it also played a part in SP-induced cellular inflammatory response. Kinetic analysis indicated that PKC isoforms induced early ERK1/2 activation, while PI3K-Akt contributed to the pathway at later time points. It was further demonstrated that PKC and PI3K-Akt were activated independent of each other. Collectively, our results suggest that SP/NK-1R activates two convergent proinflammatory signaling pathways, PKCs and PI3K-Akt, resulting in ERK1/2 and NF-kappaB activation and chemokine production in mouse macrophages.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
23
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
997-1010
|
| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19029199-Animals,
pubmed-meshheading:19029199-Cell Line,
pubmed-meshheading:19029199-Chemokines,
pubmed-meshheading:19029199-Enzyme Activation,
pubmed-meshheading:19029199-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:19029199-Inflammation,
pubmed-meshheading:19029199-Kinetics,
pubmed-meshheading:19029199-Macrophages, Peritoneal,
pubmed-meshheading:19029199-Mice,
pubmed-meshheading:19029199-NF-kappa B,
pubmed-meshheading:19029199-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19029199-Phosphorylation,
pubmed-meshheading:19029199-Protein Isoforms,
pubmed-meshheading:19029199-Protein Kinase C,
pubmed-meshheading:19029199-Protein Kinase Inhibitors,
pubmed-meshheading:19029199-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:19029199-Receptors, Neurokinin-1,
pubmed-meshheading:19029199-Substance P
|
| pubmed:year |
2009
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| pubmed:articleTitle |
Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages.
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| pubmed:affiliation |
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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