Linked Life Data

10688814

Source:http://linkedlifedata.com/resource/pubmed/id/10688814

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-3-29
pubmed:abstractText
The receptor for interleukin 5 (IL-5) consists of a cytokine-specific alpha chain (IL-5Ralpha) and a signaling beta chain, which is shared with interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). These 3 cytokines can act in eosinophil development and activation in vitro, but gene deletion or antibody blocking of IL-5 largely ablates eosinophilic responses in models of allergic disease or helminth infection. We investigated factors acting in differential IL-5Ralpha gene splicing to generate either the membrane-anchored isoform (TM-IL-5Ralpha) which associates with the common beta chain to allow IL-5 responsiveness, or a secreted, antagonist variant (SOL-IL-5Ralpha). In a murine myeloid cell line (FDC-P1), transfected with minigenes allowing expression of either IL-5Ralpha variant, IL-5 itself, but not IL-3 or GM-CSF, stimulated a reversible switch toward expression of TM-IL-5Ralpha. A switch from predominantly soluble isoform to TM-IL-5Ralpha messenger RNA (mRNA) expression was also seen during IL-5-driven eosinophil development from human umbilical cord blood-derived CD34(+) cells; this was accompanied by surface expression of IL-5Ralpha and acquisition of functional responses to IL-5. IL-3 and GM-CSF also supported eosinophil development and up-regulation of TM-IL-5Ralpha mRNA in this system, but this was preceded by expression of IL-5 mRNA and was inhibited by monoclonal antibody to IL-5. These data suggest IL-5-specific signaling, not shared by IL-3 and GM-CSF, leading to a switch toward up-regulation of functional IL-5Ralpha and, furthermore, that IL-3 and GM-CSF-driven eosinophil development is dependent on IL-5, providing an explanation for the selective requirement of IL-5 for expansion of the eosinophil lineage. (Blood. 2000;95:1600-1607)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1600-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10688814-Animals, pubmed-meshheading:10688814-COS Cells, pubmed-meshheading:10688814-Cell Differentiation, pubmed-meshheading:10688814-Cells, Cultured, pubmed-meshheading:10688814-Cercopithecus aethiops, pubmed-meshheading:10688814-Eosinophils, pubmed-meshheading:10688814-Fetal Blood, pubmed-meshheading:10688814-Gene Expression Regulation, pubmed-meshheading:10688814-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:10688814-Hematopoietic Stem Cells, pubmed-meshheading:10688814-Humans, pubmed-meshheading:10688814-Interleukin-3, pubmed-meshheading:10688814-Interleukin-5, pubmed-meshheading:10688814-Protein Conformation, pubmed-meshheading:10688814-Protein Isoforms, pubmed-meshheading:10688814-RNA, Messenger, pubmed-meshheading:10688814-Receptors, Interleukin, pubmed-meshheading:10688814-Receptors, Interleukin-5, pubmed-meshheading:10688814-Recombinant Fusion Proteins
pubmed:year
2000
pubmed:articleTitle
Interleukin 5 regulates the isoform expression of its own receptor alpha-subunit.
pubmed:affiliation
Flanders Interuniversity Institute for Biotechnology and Department of Respiratory Diseases, University of Ghent, Belgium. jan.tavernier@rug.ac.be
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't