Linked Life Data

17579082

Source:http://linkedlifedata.com/resource/pubmed/id/17579082

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-20
pubmed:abstractText
Communication between the nervous and immune systems involves the release of neuropeptides, such as calcitonin gene-related peptide (CGRP), from sensory nerves during inflammation. CGRP may inhibit the activities of both innate and adaptive immune cells, but the molecular pathways underlying this function are largely unknown. In this study, we identify CGRP as a potent inhibitor of TLR-stimulated production of inflammatory mediators, such as TNF-alpha and CCL4, by murine dendritic cells. Inhibition of TLR responses was independent of IL-10 and did not involve perturbation of canonical TLR signaling, including activation of MAPK and NF-kappaB. Instead, the inhibitory activity of CGRP was mediated by the cAMP/protein kinase A pathway leading to rapid up-regulation of the transcriptional repressor, inducible cAMP early repressor (ICER). Ectopically expressed ICER directly repressed the LPS-stimulated activity of a synthetic Tnf promoter, as well as TNF-alpha protein production driven by the endogenous promoter. Inhibition of dendritic cell gene expression by CGRP was associated with the presence of a composite cAMP response element/kappaB promoter element. In a murine model of endotoxemia, CGRP markedly attenuated serum TNF-alpha levels, and this effect was associated with the up-regulation of ICER. Together, these results establish a novel pathway for the negative regulation of TLR responses through the nervous system that critically involves induction of the transcriptional repressor ICER by the neuropeptide CGRP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
607-15
pubmed:meshHeading
pubmed-meshheading:17579082-Animals, pubmed-meshheading:17579082-Calcitonin Gene-Related Peptide, pubmed-meshheading:17579082-Cell Line, pubmed-meshheading:17579082-Cyclic AMP, pubmed-meshheading:17579082-Cyclic AMP Response Element Modulator, pubmed-meshheading:17579082-Dendritic Cells, pubmed-meshheading:17579082-Down-Regulation, pubmed-meshheading:17579082-Endotoxemia, pubmed-meshheading:17579082-Female, pubmed-meshheading:17579082-Humans, pubmed-meshheading:17579082-Lipopolysaccharides, pubmed-meshheading:17579082-Mice, pubmed-meshheading:17579082-Mice, Inbred C57BL, pubmed-meshheading:17579082-Mice, Knockout, pubmed-meshheading:17579082-Receptors, Calcitonin Gene-Related Peptide, pubmed-meshheading:17579082-Repressor Proteins, pubmed-meshheading:17579082-Toll-Like Receptors, pubmed-meshheading:17579082-Transcription, Genetic, pubmed-meshheading:17579082-Tumor Necrosis Factor-alpha
pubmed:year
2007
pubmed:articleTitle
Negative regulation of TLR responses by the neuropeptide CGRP is mediated by the transcriptional repressor ICER.
pubmed:affiliation
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, Munich, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't