Linked Life Data

18052729

Source:http://linkedlifedata.com/resource/pubmed/id/18052729

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-1-2
pubmed:abstractText
We investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on biologic signals induced by interferon-alpha (IFN-alpha) and IFN-gamma. In hematopoietic cell lines, IFN-induced signaling was investigated by Western blotting, electrophoretic mobility shift assays (EMSA), flow cytometry, protein-tyrosine phosphatase (PTP) assays, and RT-PCR. GM-CSF inhibited IFN-alpha-induced and IFN-gamma-induced Stat1 tyrosine phosphorylation in a time-dependent manner. EMSA showed that GM-CSF inhibited IFN-alpha-induced and IFN-gamma-induced IFN-gamma activator sequence (GAS) binding activity. As a consequence, IFN-induced transcription of the early response gene, IFN-stimulated gene 54 (ISG54), was inhibited. The expression of IFN regulatory factor-1 (IRF-1) and MHC class I antigens was downregulated at protein levels in hematopoietic cell lines (U937, THP1). In contrast to GM-CSF, granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) did not influence the IFN-induced Stat1 activation. To explore the molecular mechanism of suppression of Stat1 tyrosine phosphorylation, we investigated the induction and activation of cytokine-inducible SH2-containing protein/suppressor of cytokine signaling (CIS/SOCS) molecules and phosphatases on GM-CSF treatment. In contrast to G-CSF and IL-3, GM-CSF strongly induced the expression of CIS1 and SOCS2 at mRNA levels, but overexpression of CIS1 or SOCS2 in HEK293 cells did not show inhibition of Stat1 tyrosine phosphorylation upon IFN treatment. In PTP assays, on GM-CSF incubation, no enhanced src homology 2 domain tyrosine phosphatase 1 and 2 (SHP1 and SHP2) activity was detectable. However, GM-CSF-induced downregulation of Tyk2 and Jak1 tyrosine phosphorylation as well as Tyk2 protein levels likely contributed to the reduced Stat1 tyrosine phosphorylation. In hematopoietic cells, GM-CSF antagonizes IFN-induced signals by a block in Stat1 activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte Colony-Stimulating..., http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage..., http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I, http://linkedlifedata.com/resource/pubmed/chemical/IRF1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1, http://linkedlifedata.com/resource/pubmed/chemical/Interferons, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling..., http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
947-59
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cross-inhibition of interferon-induced signals by GM-CSF through a block in Stat1 activation.
pubmed:affiliation
Johannes Gutenberg-University, Department of Hematology/Oncology, Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't