Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
1994-5-16
|
| pubmed:abstractText |
Antisense oligonucleotides have proved effective in achieving targeted inhibition of gene expression. In such experiments, sense oligonucleotides have frequently been used as a control for nonspecific effects, but the results have been variable, raising questions about the reliability of sense oligomers as a control. It is possible that some of the effects of sense oligonucleotides may be specific. We have shown that phosphorothioate antisense oligonucleotides to the p65 subunit of NF-kappa B, a transcription factor, cause a block in cell adhesion. In our efforts to test the efficacy of NF-kappa B p65 oligonucleotides in vivo, we unexpectedly observed that the control p65-sense, but not the p65-antisense, oligonucleotides caused massive splenomegaly in mice. In the current study we demonstrate a sequence-specific stimulation of splenic cell proliferation, both in vivo and in vitro, by treatment with p65-sense oligonucleotides. Cells expanded by this treatment are primarily B-220+, sIg+ B cells. The secretion of immunoglobulins by the p65-sense oligonucleotide-treated splenocytes is also enhanced. In addition, the p65-sense-treated splenocytes, but not several other cell lines, showed an upregulation of NF-kappa B-like activity in the nuclear extracts, an effect not dependent on new protein or RNA synthesis. These results demonstrate that phosphorothioate oligonucleotides can exert sequence-specific effects in vivo, irrespective of sense or antisense orientation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides
|
| pubmed:status |
MEDLINE
|
| pubmed:issn |
1050-5261
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
309-22
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8155973-Animals,
pubmed-meshheading:8155973-B-Lymphocytes,
pubmed-meshheading:8155973-Base Sequence,
pubmed-meshheading:8155973-Binding Sites,
pubmed-meshheading:8155973-Cell Adhesion,
pubmed-meshheading:8155973-Cell Division,
pubmed-meshheading:8155973-Cells, Cultured,
pubmed-meshheading:8155973-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:8155973-Flow Cytometry,
pubmed-meshheading:8155973-Immunoglobulin G,
pubmed-meshheading:8155973-Immunoglobulin M,
pubmed-meshheading:8155973-Lymphocyte Activation,
pubmed-meshheading:8155973-Mice,
pubmed-meshheading:8155973-Mice, Inbred C57BL,
pubmed-meshheading:8155973-Molecular Sequence Data,
pubmed-meshheading:8155973-NF-kappa B,
pubmed-meshheading:8155973-Oligodeoxyribonucleotides,
pubmed-meshheading:8155973-Spleen,
pubmed-meshheading:8155973-Splenomegaly,
pubmed-meshheading:8155973-Thionucleotides,
pubmed-meshheading:8155973-Up-Regulation
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
A sense phosphorothioate oligonucleotide directed to the initiation codon of transcription factor NF-kappa B p65 causes sequence-specific immune stimulation.
|
| pubmed:affiliation |
Department of Inflammation/Autoimmune Diseases, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, New Jersey 07110.
|
| pubmed:publicationType |
Journal Article
|