Linked Life Data

10591154

Source:http://linkedlifedata.com/resource/pubmed/id/10591154

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-12-22
pubmed:abstractText
Depending on base sequence, DNA displays immunological activities relevant to the design of novel therapeutic agents. To determine the influence of backbone structure on these activities, we tested a series of synthetic phosphodiester and phosphorothioate oligonucleotides in in vitro cultures of murine spleen cells. These compounds were 30 bases long and consisted of either a single base or an immunostimulatory sequence (AACGTT) flanked on 5' and 3' ends by 12 nucleotides of each base. Cell activation was assessed by both thymidine incorporation and expression of cell surface CD69; production of interleukin-6 and interleukin-12 was used as a measure of cytokine stimulation. In these assays, phosphorothioate oligonucleotides induced much higher levels of proliferation, CD69 expression, and cytokine production than the comparable phosphodiester compounds and had activity at lower concentrations. The sequence for optimal stimulation by phosphorothioates varied among responses, however. For example, whereas compounds containing an immunostimulatory sequence all induced similar levels of proliferation and CD69 expression, cytokine production was greatest with compounds with dA and dT flanks. Furthermore, while single base dG oligonucleotides stimulated proliferation as both phosphodiesters and phosphorothioates, they failed to stimulate cytokine production. Together, these findings indicate that base sequence as well as backbone chemistry influence immune activation by synthetic oligonucleotides, with the effects varying among responses. While suggesting differences in the structure-function relationships of nucleic acids in their immune activities, these findings also raise the possibility of the design of agents with specific patterns of immune modulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1981-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Influence of backbone chemistry on immune activation by synthetic oligonucleotides.
pubmed:affiliation
Medical Research Service, Durham Veterans Administration Hospital, Durham, NC 27705, USA. dpiset@acpub.duke.edu
pubmed:publicationType
Journal Article, In Vitro