Linked Life Data

9147372

Source:http://linkedlifedata.com/resource/pubmed/id/9147372

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
1997-7-23
pubmed:abstractText
The proinflammatory cytokine, interleukin-1 (IL-1) is elevated in the Alzheimer's disease (AD) brain. Studies from our laboratory have demonstrated that beta-amyloid (A beta) 1-42, fibrillar A beta 1-40 and A beta 25-35 induce the release of IL-1 beta from activated THP-1 cells, a human monocyte cell line. A beta also is chemotactic for primary rodent microglia and peritoneal macrophages. We hypothesize that A beta is a chemokine and induces these responses by interaction with chemotactic receptors. If this is true, then these A beta-induced responses should be calcium-dependent and require activation of pertussis toxin-sensitive G-proteins. To test this hypothesis, THP-1 cells were grown in culture with lipopolysaccharide (LPS) and incubated with A beta 1-42 (5 muM) in the presence and absence of a calcium chelator, an inhibitor of intracellular calcium mobilization, a calcium channel blocker, or pertussis toxin, a bacterial endotoxin which uncouples G proteins from receptors by catalyzing the ADP ribosylation of cysteine near the carboxy-terminus of the alpha subunit. The media was collected and IL-1 beta present in the media was measured using an ELISA. Treatment of LPS-activated THP-1 cells with A beta 1-42 significantly elevated IL-1 beta released into the media as previously shown. Addition or ethylene glycol-bis (beta-aminothyl ether) N,N,N'N'-tetraacetic acid (EGTA) (0.5 mM), a calcium chelator, to the media blocked A beta-induced IL-1 beta release, but had no effect on LPS-activated THP-1 cell release of IL-1 beta. The presence of 3,4,5-trimethoxybenzoic acid 8-(diethyl amino)-octyl ester (TMB-8), an inhibitor of intracellular calcium mobilization, as well as nickel chloride, a non-specific calcium channel blocker, in the media also inhibited A beta-induced IL-1 release from LPS-activated THP-1 cells. IL- 1 beta release from activated THP-1 monocytes incubated with TMB-8 and nickel chloride without A beta remained at baseline values. Pretreatment of THP-1 monocytes with pertussis toxin for 4 h, followed by LPS activation and incubation with A beta, antagonized the release of IL-1 beta from these cells, but did not alter IL-1 beta release from activated THP-1 monocytes. These data suggest that A beta-induced IL-1 beta release from these cells is calcium-dependent and requires the activation of specific G-proteins. These findings are consistent with known second messengers that are activated following stimulation of chemotactic receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/8-(N,N-diethylamino)octyl-3,4,5-trim..., http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Gallic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Mitogens, http://linkedlifedata.com/resource/pubmed/chemical/Nickel, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella, http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42), http://linkedlifedata.com/resource/pubmed/chemical/nickel chloride
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0047-6374
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
199-211
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
beta-Amyloid-induced IL-1 beta release from an activated human monocyte cell line is calcium- and G-protein-dependent.
pubmed:affiliation
Hoover Arthritis Research Center, Sun Health Research Institute, Sun City, AZ 85372, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't