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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-7-8
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pubmed:abstractText |
Human formyl peptide receptor-like 1 and its mouse homologue formyl peptide receptor 2 (FPR2) are G protein-coupled receptors used by a number of exogenous and host-derived chemotactic peptides, including the 42 aa form of beta amyloid peptide, a causative factor of Alzheimer's disease. Functional FPR2 was induced by bacterial LPS in murine microglial cells, the resident phagocytic cells that play a pivotal role in inflammatory and immunological diseases in the CNS. To identify agents that may suppress microglial cell activation under proinflammatory conditions, we investigated the effect of TGF-beta1 on the expression of functional FPR2 by microglial cells activated by LPS. TGF-beta1 dose-dependently inhibited the mRNA expression and function of FPR2 in LPS-activated microglial cells. The inhibitory effect of TGF-beta1 was mediated by Smad3, a key signaling molecule coupled to the TGF-beta receptor, and the transcription coactivator, p300. Also, TGF-beta1 activates MAPKs in microglial cells that became refractory to further stimulation by LPS. These effects of TGF-beta1 culminate in the inhibition of LPS-induced activation of NF-kappaB and the up-regulation of FPR2 in microglial cells. Thus, TGF-beta1 may exert a protective role in CNS diseases characterized by microglial cell activation by proinflammatory stimulants.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E1A-Associated p300 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Ep300 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Formyl Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/formyl peptide receptor 2, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
962-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15240683-Animals,
pubmed-meshheading:15240683-DNA-Binding Proteins,
pubmed-meshheading:15240683-E1A-Associated p300 Protein,
pubmed-meshheading:15240683-Lipopolysaccharides,
pubmed-meshheading:15240683-Mice,
pubmed-meshheading:15240683-Microglia,
pubmed-meshheading:15240683-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15240683-NF-kappa B,
pubmed-meshheading:15240683-Nuclear Proteins,
pubmed-meshheading:15240683-Receptors, Formyl Peptide,
pubmed-meshheading:15240683-Smad3 Protein,
pubmed-meshheading:15240683-Trans-Activators,
pubmed-meshheading:15240683-Transforming Growth Factor beta,
pubmed-meshheading:15240683-Transforming Growth Factor beta1
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pubmed:year |
2004
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pubmed:articleTitle |
TGF-beta1 disrupts endotoxin signaling in microglial cells through Smad3 and MAPK pathways.
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pubmed:affiliation |
Laboratory of Molecular Immunoregulation, Center for Cancer Research, and Basic Research Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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