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Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein.

Iwata, Mineo and Graf, Lynn and Awaya, Norihiro and Torok-Storb, Beverly (2002) Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein. Blood, 100 (4). pp. 1318-25. ISSN 0006-4971

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Abstract

DNA spotted microarrays were used to compare gene expression profiles from 2 functionally distinct human marrow stromal cell lines: HS-27a, which supports cobblestone area formation by early hematopoietic progenitors, and HS-5, which secretes multiple cytokines that support the proliferation of committed progenitors. One unexpected result was the high level of interleukin-7 receptor (IL-7R) gene expression in HS-27a stromal cells. Northern blot analysis confirmed the IL-7R RNA expression, and Western blots for the IL-7R protein detected both a full-length (90-kd) IL-7R and a smaller 30-kd fragment in both HS-27a cells and primary stromal cell cultures, whereas only the 90-kd receptor protein was detected in peripheral blood mononuclear cells. Biotinylated IL-7 was shown to bind to HS-27a cells under physiologic conditions, and this binding was inhibited by blocking anti-IL-7 antibodies. Tyrosine phosphorylation of several proteins (55 kd, 30 kd, and 24 kd) in HS-27a cells was rapidly increased after incubation with recombinant IL-7. One of the phosphorylated proteins proved to be the 30-kd IL-7R fragment. Exposure of HS-27a cells to IL-7 resulted in a 10-fold increase in secretion of IL-6 into culture supernatants but no increase in the cytokines stromal cell-derived factor 1, macrophage inflammatory protein 1 alpha, or IL-1 beta. The up-regulation of IL-6 secretion is associated with a rapid but transient increase in detectable levels of IL-6 messenger RNA. These data suggest that IL-7 may function to regulate the milieu of the microenvironment by modulating IL-6 secretion by the IL-7R-expressing stromal elements.

Item Type: Article
DOI: 10.1182/blood-2002-01-0062
PubMed ID: 12149213
Keywords or MeSH Headings: Antibodies/pharmacology; Blotting, Northern; Blotting, Western; Bone Marrow Cells/metabolism; Cell Division; Cell Line; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Gene Expression; Humans; Interleukin-6/genetics/secretion; Interleukin-7/immunology/metabolism/pharmacology; Phosphorylation; Phosphotyrosine/metabolism; RNA, Messenger/analysis; Receptors, Interleukin-7/genetics/metabolism; Recombinant Proteins/metabolism/pharmacology; Stromal Cells/metabolism;
Depositing User: Library Staff
Date Deposited: 22 Dec 2011 20:12
Last Modified: 14 Feb 2012 14:44
URI: http://authors.fhcrc.org/id/eprint/509

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