|
|
Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-01-0062.
Submitted January 9, 2002
Accepted May 13, 2002
Functional interleukin-7 receptors (IL7R) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein
Mineo Iwata*, Lynn Graf, Norihiro Awaya, and Beverly Torok-Storb
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
* Corresponding author; email: miwata{at}fhcrc.org.
DNA spotted microarrays were used to compare gene expression profiles from two 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 (IL7R) gene expression in HS-27a stromal cells. Northern blot analysis confirmed the IL7R RNA expression, and Western blots for the IL7R protein detected both a full-length (90-kd) IL7R 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 physiological 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 IL7R fragment. Exposure of HS-27a cells to IL-7 resulted in a 10-fold increase in secretion of interleukin-6 (IL-6) into culture supernatants but no increase in the cytokines SDF-1, MIP-1a or IL-1b. The up-regulation of IL-6 secretion is associated with a rapid but transient increase in detectable levels of IL-6 mRNA. These data suggest that IL-7 may function to regulate the milieu of the microenvironment by modulating IL-6 secretion by the IL7R expressing stromal elements.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. E. Perez, N. Parquet, K. Shain, R. Nimmanapalli, M. Alsina, C. Anasetti, and W. Dalton
Bone Marrow Stroma Confers Resistance to Apo2 Ligand/TRAIL in Multiple Myeloma in Part by Regulating c-FLIP
J. Immunol.,
February 1, 2008;
180(3):
1545 - 1555.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Giuliani, S. Colla, F. Morandi, M. Lazzaretti, R. Sala, S. Bonomini, M. Grano, S. Colucci, M. Svaldi, and V. Rizzoli
Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation
Blood,
October 1, 2005;
106(7):
2472 - 2483.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Iwata, N. Awaya, L. Graf, C. Kahl, and B. Torok-Storb
Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells
Blood,
June 15, 2004;
103(12):
4496 - 4502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Graf, M. Iwata, and B. Torok-Storb
Gene expression profiling of the functionally distinct human bone marrow stromal cell lines HS-5 and HS-27a
Blood,
July 30, 2002;
100(4):
1509 - 1511.
[Full Text]
[PDF]
|
|
|
|
|
