Linked Life Data

20871625

Source:http://linkedlifedata.com/resource/pubmed/id/20871625

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-2
pubmed:abstractText
Lymphocyte activation leads to changes in chemokine receptor expression. There are limited data, however, on how lymphocyte activators can alter chemokine signaling by affecting downstream pathways. We hypothesized that B cell-activating agents might alter chemokine responses by affecting downstream signal transducers, and that such effects might differ depending on the activator. We found that activating mouse B cells using either anti-IgM or lipopolysaccharide (LPS) increased the surface expression of CCR6 and CCR7 with large increases in chemotaxis to their cognate ligands. By contrast, while anti-IgM also led to enhanced calcium responses, LPS-treated cells showed only small changes in calcium signaling as compared with cells that were freshly isolated. Of particular interest, we found that LPS caused a reduction in the level of B-cell phospholipase C (PLC)-?2 mRNA and protein. Data obtained using PLC-?2(-/-) mice showed that the ?2 isoform mediates close to one-half the chemokine-induced calcium signal in resting and anti-IgM-activated B cells, and we found that calcium signals in the LPS-treated cells were boosted by increasing the level of PLC-?2 using transfection, consistent with a functional effect of downregulating PLC-?2. Together, our results show activator-specific effects on responses through B-cell chemokine receptors that are mediated by quantitative changes in a downstream signal-transducing protein, revealing an activity for LPS as a downregulator of PLC-?2, and a novel mechanism for controlling chemokine-induced signals in lymphocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
2042-0226
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
428-39
pubmed:dateRevised
2011-5-5
pubmed:meshHeading
pubmed-meshheading:20871625-Animals, pubmed-meshheading:20871625-B-Lymphocytes, pubmed-meshheading:20871625-Calcium, pubmed-meshheading:20871625-Calcium Signaling, pubmed-meshheading:20871625-Chemokines, pubmed-meshheading:20871625-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:20871625-Down-Regulation, pubmed-meshheading:20871625-Gene Expression Regulation, Enzymologic, pubmed-meshheading:20871625-Immunoglobulin M, pubmed-meshheading:20871625-Lipopolysaccharides, pubmed-meshheading:20871625-Lymphocyte Activation, pubmed-meshheading:20871625-Mice, pubmed-meshheading:20871625-Models, Immunological, pubmed-meshheading:20871625-Phospholipase C beta, pubmed-meshheading:20871625-RNA, Messenger, pubmed-meshheading:20871625-Receptors, Chemokine, pubmed-meshheading:20871625-Signal Transduction, pubmed-meshheading:20871625-Type C Phospholipases
pubmed:year
2010
pubmed:articleTitle
Pathway-selective suppression of chemokine receptor signaling in B cells by LPS through downregulation of PLC-?2.
pubmed:affiliation
Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural