Linked Life Data

11591715

Source:http://linkedlifedata.com/resource/pubmed/id/11591715

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
50
pubmed:dateCreated
2001-12-12
pubmed:abstractText
In the vessel wall, macrophages are among the cells that upon activation contribute to the atherosclerotic process. Low density lipoproteins (LDL) can mediate this activation but only after enzymatic or oxidative modification. Lipoprotein(a) (Lp(a)) is an LDL variant that has been shown to have an atherogenic potential by no clearly established mechanisms. In the present study we examined whether native Lp(a) can activate macrophages and, if so, identify the structural elements involved in this action. For this purpose, we utilized human THP-1 macrophages, prepared by treating THP-1 monocytes with phorbol ester, and we exposed them to Lp(a) and its two derivatives, apo(a)-free LDL (Lp(a-)) and free apo(a). We also studied apo(a) fragments, F1 (N terminus) and F2 (C terminus) and subfragments thereof, obtained by leukocyte elastase digestion. By Northern blot analyses, Lp(a), but not Lp(a-), caused up to a 12-fold increase in interleukin 8 (IL-8) mRNA as compared with untreated cells. Free apo(a) also induced the production of IL-8 mRNA; however, the effect was 3-4-fold higher than that of Lp(a). The increase in mRNA was associated with the accumulation of IL-8 protein in the culture medium. F1 had only a minimal effect, whereas F2 was 1.5-2-fold more potent than apo(a), an activity mostly contained in the Kringle V-protease region. A monoclonal antibody specific for Kringle V inhibited the apo(a)-mediated effect on IL-8. We conclude that Lp(a) via elements contained in the C-terminal domain of apo(a) causes in THP-1 macrophages an increased production of IL-8, a chemokine with pro-inflammatory properties, an event that may be relevant to the process of atherosclerosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46864-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11591715-Adjuvants, Immunologic, pubmed-meshheading:11591715-Antibodies, Monoclonal, pubmed-meshheading:11591715-Apolipoproteins A, pubmed-meshheading:11591715-Blotting, Northern, pubmed-meshheading:11591715-Cell Line, pubmed-meshheading:11591715-Cholera Toxin, pubmed-meshheading:11591715-Dose-Response Relationship, Drug, pubmed-meshheading:11591715-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:11591715-Humans, pubmed-meshheading:11591715-Interleukin-8, pubmed-meshheading:11591715-Leukocyte Elastase, pubmed-meshheading:11591715-Macrophages, pubmed-meshheading:11591715-Phorbol Esters, pubmed-meshheading:11591715-Protein Structure, Tertiary, pubmed-meshheading:11591715-RNA, pubmed-meshheading:11591715-RNA, Messenger, pubmed-meshheading:11591715-Time Factors, pubmed-meshheading:11591715-Transcription, Genetic, pubmed-meshheading:11591715-Virulence Factors, Bordetella
pubmed:year
2001
pubmed:articleTitle
Stimulation of interleukin-8 production in human THP-1 macrophages by apolipoprotein(a). Evidence for a critical involvement of elements in its C-terminal domain.
pubmed:affiliation
Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC5041, Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.