Linked Life Data

9166774

Source:http://linkedlifedata.com/resource/pubmed/id/9166774

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1997-6-23
pubmed:abstractText
Tumor necrosis factor alpha (TNF alpha), a polypeptide produced by activated macrophages, is a highly pleiotropic cytokine which elicits inflammatory and immunological reactions. The binding of TNF alpha to tumor necrosis factor receptor type I (TNFRI) is considered the initial step responsible for some of the multiple biological functions mediated by TNF alpha. The role of TNF alpha as an inflammatory mediator through human TNFRI makes TNFRI an attractive target for intervention in both acute and chronic inflammatory diseases. In this study, we have identified partial phosphorothioate oligodeoxyribonucleotides (ODNs) containing C-5 propynyl or hexynyl derivatives of 2'-deoxyuridine which specifically inhibited TNFRI and subsequently inhibited the functions of TNF alpha mediated through TNFRI. The most active ODNs were directed against the 3'-poly adenylation signal site on the TNFRI mRNA, and in a cellular assay, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations, in the presence of Cellfectin. The inhibition of gene expression correlated with the binding affinity of the ODN for the target mRNA. The ODNs lowered TNFRI protein levels and TNF alpha-mediated functions by specifically reducing levels of TNFRI mRNA. These anti-TNFRI ODNs offer a novel approach for controlling biological functions of TNF alpha and may be useful as human therapeutic agents for treating diseases in which TNF alpha has been implicated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6033-45
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9166774-Antigens, CD, pubmed-meshheading:9166774-Cells, Cultured, pubmed-meshheading:9166774-Dose-Response Relationship, Drug, pubmed-meshheading:9166774-Drug Design, pubmed-meshheading:9166774-Fibroblasts, pubmed-meshheading:9166774-Gene Expression, pubmed-meshheading:9166774-Humans, pubmed-meshheading:9166774-Interleukin-6, pubmed-meshheading:9166774-Interleukin-8, pubmed-meshheading:9166774-Oligonucleotides, Antisense, pubmed-meshheading:9166774-RNA, Messenger, pubmed-meshheading:9166774-RNA Processing, Post-Transcriptional, pubmed-meshheading:9166774-Receptors, Tumor Necrosis Factor, pubmed-meshheading:9166774-Receptors, Tumor Necrosis Factor, Type I, pubmed-meshheading:9166774-Receptors, Tumor Necrosis Factor, Type II, pubmed-meshheading:9166774-Thionucleotides, pubmed-meshheading:9166774-Toxicity Tests, pubmed-meshheading:9166774-Tumor Necrosis Factor-alpha
pubmed:year
1997
pubmed:articleTitle
Modified antisense oligonucleotides directed against tumor necrosis factor receptor type I inhibit tumor necrosis factor alpha-mediated functions.
pubmed:affiliation
Aronex Pharmaceuticals, Inc., The Woodlands, Texas 77381-4223, USA. jojwang@aronex.com
pubmed:publicationType
Journal Article, Comparative Study