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
| Autor: | Lynn Graf, Beverly Torok-Storb, Mineo Iwata, Norihiro Awaya |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Stromal cell
medicine.medical_treatment Blotting Western Immunology Gene Expression Bone Marrow Cells Biology Biochemistry Antibodies Cell Line chemistry.chemical_compound Cell–cell interaction Gene expression medicine Humans RNA Messenger Northern blot Phosphorylation Phosphotyrosine Cells Cultured Messenger RNA Receptors Interleukin-7 Interleukin-6 Interleukin-7 Tyrosine phosphorylation Cell Biology Hematology Blotting Northern Molecular biology Recombinant Proteins Blot Cytokine chemistry Electrophoresis Polyacrylamide Gel Stromal Cells Cell Division |
| Zdroj: | Blood. 100:1318-1325 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2002-01-0062 |
| Popis: | 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 1α, or IL-1β. 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. |
| Databáze: | OpenAIRE |
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