Linked Life Data

21210814

Source:http://linkedlifedata.com/resource/pubmed/id/21210814

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-3-1
pubmed:abstractText
The survival and death rates of inflammatory cells directly control their number and are substantially associated with the degree of inflammation. Microglia, key players in neuroinflammation, often cause excessive reactions implicated in neurological diseases. However, the mechanisms that determine microglial fate under pathological conditions remain to be elucidated. Here, we report that activation by lipopolysaccharide (LPS, a Toll-like receptor 4 ligand), an inflammation inducer, primarily promotes survival of microglia, but as its concentration is increased it induces cell death, resulting in decreased cell number. Moreover, extracellular ATP, which is released upon tissue damage, further enhanced the survival induced by a low LPS concentration and the death induced by a high LPS concentration. The survival-promoting effect of ATP was mimicked by non-hydrolyzable ATP analog, adenosine 5'-O-(3-thiotriphosphate), and also by the P2X(7) receptor agonist, 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, and was suppressed by the P2X(7) antagonists, Brilliant Blue G and A 438079. On the contrary, the death of LPS-activated microglia was not affected by adenosine 5'-O-(3-thiotriphosphate), but enhanced by adenosine, ATP breakdown product. Thus, extracellular ATP modulates microglial survival and death in different ways involving P2X(7) receptor activation and ATP degradation to adenosine, respectively. Such Toll-like receptor 4/purinergic signaling may provide a fine regulatory system of neuroinflammation through modulating the microglial cell number.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1471-4159
pubmed:author
pubmed:copyrightInfo
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
pubmed:issnType
Electronic
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1138-47
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Extracellular ATP differentially modulates Toll-like receptor 4-mediated cell survival and death of microglia.
pubmed:affiliation
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't