Linked Life Data

11521069

Source:http://linkedlifedata.com/resource/pubmed/id/11521069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-8-24
pubmed:abstractText
The synthetic antagonists of lipopolysaccharide (LPS), E5531 and E5564, are analogs of the lipid A portion of LPS that not only lack agonistic activity but also inhibit the biological effects of LPS both in vitro and in vivo. The effects of LPS and these synthetic antagonists have been localized to the recently described Toll-like receptor 4 (TLR4). A recent report indicated that the naturally occurring LPS antagonist Rhodobacter sphaeroides LPS loses its antagonist properties and gains pro-inflammatory qualities in the presence of chlorpromazine and other amphipathic drugs. To determine whether these reported actions occur with our chemically defined LPS antagonists, we examined the effects of chlorpromazine, fluphenazine, trifluoperazine, and lidocaine on the antagonism elicited by RsLPS and E5531 in U373 cells, which produce IL-6 in response to LPS. We also tested the effects of these amphipathic molecules on the LPS-neutralizing activity of RsLPS and E5564 on LPS-induced TNF-alpha release in human whole blood. The results indicate that neither chlorpromazine, fluphenazine, trifluoperazine nor lidocaine alter the activity of E5531 or E5564 in an in vitro cell system or human whole blood. Furthermore, chlorpromazine did not affect the antagonistic activity of RsLPS or E5564 on IL-6 generation by peripheral blood mononuclear cells. Thus, based on these data, our purified synthetic LPS-antagonists do not appear to lose their antagonistic properties and/or become agonists in the presence of amphipathic agents or drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0968-0519
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
447-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Examination of chlorpromazine and other amphipathic drugs on the activity of lipopolysaccharide antagonists, E5564 and E5531.
pubmed:affiliation
Department of Molecular Biology/Biochemistry and Pharmacology, Signal Transduction Research, and Synthetic Chemistry, Eisai Research Institute, Wilmington, MA, USA.
pubmed:publicationType
Journal Article, In Vitro