Linked Life Data

9002958

Source:http://linkedlifedata.com/resource/pubmed/id/9002958

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-2-24
pubmed:abstractText
Activation of T-cell hybridomas, preactivated normal T cells, and peripheral blood lymphocytes (PBL) from human immunodeficiency virus (HIV)-infected individuals results in apoptosis. In the first two cases, apoptosis is caused by the upregulation of Fas ligand (FasL) and its subsequent interaction with Fas; the mechanism for the spontaneous and activation-induced death of lymph node cells and PBL from HIV+ blood is not known. A number of protease inhibitors have been shown to prevent T-cell apoptosis under all of these circumstances, but the mechanism of action has not been determined. Here we show that the cysteine protease inhibitor E64d prevent activation-induced T hybridoma cell death by inhibiting the upregulation of FasL. Quantitative polymerase chain reaction (PCR) demonstrated that mRNA for FasL is expressed at low levels in fresh PBL from HIV-infected blood, but increases in cultured PBL from both uninfected and HIV-infected donors. The ex vivo apoptosis of PBL from HIV+ donors was prevented by adding the soluble extracellular domain of Fas, demonstrating a requisite role for Fas/ FasL interactions in this form of cell death. Furthermore, while having no effect on the death of PBL from HIV-infected blood stimulated directly via Fas, E64d inhibited FasL upregulation. Thus, aberrant apoptosis of cultured PBL from HIV-infected individuals is mediated by FasL and Fas, and E64d blocks this apoptosis by inhibiting the upregulation of FasL. These results are consistent with the hypothesis that the abnormal expression of Fas and the inducible expression of FasL, contributes to the immunodeficiency of patients with acquired immune deficiency syndrome and suggest that modulation of FasL expression could be an effective target for therapeutic intervention.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
550-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
A cysteine protease inhibitor prevents activation-induced T-cell apoptosis and death of peripheral blood cells from human immunodeficiency virus-infected individuals by inhibiting upregulation of Fas ligand.
pubmed:affiliation
Laboratory of Immune Cell Biology, National Cancer Institute, Bethesda, MD 20892-1152, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't