Linked Life Data

15320959

Source:http://linkedlifedata.com/resource/pubmed/id/15320959

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-8-23
pubmed:abstractText
The pleiotropic biologic effects of interferon (IFN) are mediated through regulation of the expression of numerous IFN-sensitive genes. Peripheral blood mononuclear cells (PBMCs) obtained from healthy donors were analyzed to study the immunoregulatory and antiviral messenger RNAs (mRNAs) and proteins regulated by pegylated IFN-alpha2b (PEG-IFN-alpha2b) and IFN-alpha2b. A dose-dependent and time-dependent response for multiple IFN-regulated genes was observed. IFN-dependent protein production and secretion were correlated with IFN-regulated mRNA induction. Overall regulation of gene expression patterns for PEG-IFN-alpha2b and IFN-alpha2b was comparable, even though the antiviral activity of PEG-IFN-alpha2b demonstrated a longer biologic halflife in vitro compared with IFN-alpha2b. To study the heterogeneity of responses, PBMCs obtained from over 25 healthy donors were analyzed. Within a particular donor dataset, gene-specific and dose-dependent responses to PEG-IFN-alpha2b treatment, demonstrated in both the amplitude of transcriptional upregulation and the duration of sustained mRNA upregulation, were observed. However because of donor heterogeneity, the amplitude of a given transcriptional response could not be predicted for a specific dose of PEG-IFN-alpha2b. Notably, mRNA levels of oligoadenylate synthetase (OAS), double-stranded RNA (dsRNA)-activated protein kinase (PKR), IP-10, IFN-stimulated gene 54 (ISG54), and ISG15 were upregulated after 120 h of continuous PEG-IFN-alpha2b treatment. These results suggest that the use of antiviral and immunoregulatory protein mRNA levels as markers to assess the therapeutic efficacy of IFN-alpha2b and PEG-IFN-alpha2b against viral and neoplastic diseases in clinical trials is promising but will require further analysis using clinical patient samples.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
455-69
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Regulation of gene expression by pegylated IFN-alpha2b and IFN-alpha2b in human peripheral blood mononuclear cells.
pubmed:affiliation
Department of Biotechnology, Schering-Plough Research Institute, Union, NJ 07083, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.