Linked Life Data

11034083

Source:http://linkedlifedata.com/resource/pubmed/id/11034083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2000-10-16
pubmed:abstractText
Recombinant human IFN alpha (rhIFN-alpha) plays an important role in the treatment of hairy cell leukemia (HCL). However, the mechanisms leading to its beneficial effect are not completely clarified, and there is no information on IFN-alpha gene expression in this disease. Therefore, we investigated the pattern of IFN-alpha gene expression and protein production in HCL and their potential regulation by rhIFN-alpha. Blood samples from 10 patients with HCL and 8 healthy donors (HD) were investigated. Expression of IFN-alpha mRNA was assessed by reverse transcription-PCR analysis in peripheral blood mononuclear cells (PBMCs) under basal conditions and on induction with rhIFN-alpha and polyionosinic-polycytidylic acid [poly(I.C)]. IFN-alpha concentrations in plasma and culture supernatants were measured by immunoassays, and intracellular IFN-alpha was evaluated by fluorescence-activated cell sorting analysis. Results showed that, in contrast to blood samples from HDs, freshly isolated PBMCs from un treated HCL patients did not express IFN-alpha mRNA, whereas IFN-alpha transcripts were found in patients who were under rhIFN-alpha therapy Plasma of untreated patients contained no, or extremely low levels of IFN-alpha as compared with plasma of treated patients and HDs. Ex vivo treatment of PBMCs with rhIFN-alpha or poly(I.C) resulted in a remarkable up-regulation of IFN-alpha at the mRNA and protein level. In HCL, however the amounts of IFN-alpha protein remained less than in HD. Inhibition of IFN-alpha transcription was found after exposure of PBMCs to serum fron untreated patients. Finally, a reduced capacity to produce IFN-alpha was found within B- cell, T-cell, and monocyte compartments in HCL patients which could be enhanced by rhIFN-alpha. The results demonstrate the ability, of rhIFN-alpha to up-regulate the expression of IFN-alpha gene and protein production and suggest that priming the production of endogenous IFN-alpha is a critical step in the mechanism of action of rhIFN-alpha in HCL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5420-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11034083-Aged, pubmed-meshheading:11034083-Aged, 80 and over, pubmed-meshheading:11034083-Antineoplastic Agents, pubmed-meshheading:11034083-B-Lymphocytes, pubmed-meshheading:11034083-Cells, Cultured, pubmed-meshheading:11034083-Female, pubmed-meshheading:11034083-Gene Expression Regulation, Leukemic, pubmed-meshheading:11034083-Humans, pubmed-meshheading:11034083-Interferon Inducers, pubmed-meshheading:11034083-Interferon Type I, pubmed-meshheading:11034083-Interferon-alpha, pubmed-meshheading:11034083-Kinetics, pubmed-meshheading:11034083-Leukemia, Hairy Cell, pubmed-meshheading:11034083-Leukocytes, Mononuclear, pubmed-meshheading:11034083-Male, pubmed-meshheading:11034083-Middle Aged, pubmed-meshheading:11034083-Poly I-C, pubmed-meshheading:11034083-RNA, Messenger, pubmed-meshheading:11034083-Recombinant Proteins
pubmed:year
2000
pubmed:articleTitle
Reconstitution of endogenous interferon a by recombinant interferon in hairy cell leukemia.
pubmed:affiliation
University of Vienna, Clinic of Internal Medicine 1, Department of Hematology, L. Boltzmann Institute for Cytokine Research, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't