Linked Life Data

19390489

Source:http://linkedlifedata.com/resource/pubmed/id/19390489

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-7-21
pubmed:abstractText
During infections, pathogens bind to toll-like receptor (TLR)4 and CD14 receptors and induce cytokine release, leading to inflammation. Here, we investigated TLR4 and CD14 expression on peripheral blood leukocytes (PBLs) and their roles in lipopolysaccharide (LPS)-induced cytokine and chemokine release. Full-term and preterm neonates and adults were studied. PBLs were pretreated with anti-TLR4- and anti-CD14-blocking antibodies and stimulated with LPS. Cytokine and chemokine levels were measured in supernatants. TLR4, CD14 expression, and LPS-induced CXCL8 release were higher in neonates, possibly contributing to aberrant inflammation. TLR4 blockade resulted in approximately 3-fold greater suppression of LPS-induced CXCL8 release in preterm neonates (38%) than in adults (14%). CD14 blockade (approximately 80%) in neonates induced approximately 3-fold greater inhibition of CXCL8 release, compared with anti-TLR4 (approximately 30%). Anti-TLR4 partly (50-60%) inhibited IL-10 and TNF-alpha, whereas anti-CD14 completely suppressed their release. Our findings reveal that neonates depend more on TLR4 for CXCL8 release. Furthermore, neonatal LPS-induced CXCL8 release, apart from TLR4/CD14-mediated signaling, is regulated by LPS interactions with other TLRs and/or immune receptors. IL-10 and TNF-alpha release depends on LPS binding not only to CD14/TLR4 but also to CD14 associated with another TLR. Our findings reveal the contribution of TLR4 and CD14 in neonatal cytokine and chemokine release and could aid in design of antagonists to prevent harmful inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1530-0447
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
179-84
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Distinct roles of TLR4 and CD14 in LPS-induced inflammatory responses of neonates.
pubmed:affiliation
Neonatal Immunology Laboratory, B'Neonatal Intensive Care Unit, Aghia Sophia Children's Hospital, Athens 115 27, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't