|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 September 2000, Vol. 96, No. 6, pp. 2093-2099
HEMATOPOIESIS
Interferon- directly represses megakaryopoiesis by inhibiting
thrombopoietin-induced signaling through induction of
SOCS-1
Qin Wang,
Yoshitaka Miyakawa,
Norma Fox, and
Kenneth Kaushansky
From the Division of Hematology, University of
Washington School of Medicine, Seattle, WA.
Interferon (IFN)- has proven useful for treating several
clinical conditions, including chronic viral hepatitis and chronic myeloproliferative and lymphoproliferative disorders. In addition to
its well-known antiviral effects, the cytokine exerts antiproliferative effects on many cell types, helping to explain its therapeutic usefulness in these latter conditions. However, this same property accounts for several undesirable effects, including thrombocytopenia, which can interfere with the successful clinical application of IFN-. Unfortunately, the mechanisms responsible for the
myelosuppressive effects of the cytokine are incompletely understood.
The effects of IFN- on megakaryocyte (MK) development were studied.
Using several marrow cell purification techniques and quantitative
culture methods, it was found that IFN- directly inhibits
thrombopoietin (TPO)-induced MK growth. Previous studies indicated
that Janus kinase (JAK) and its substrates mediate the effects of
TPO on cellular proliferation and survival. It was found that IFN-
directly suppresses TPO-induced phosphorylation of the JAK2 substrates c-Mpl and STAT 5 in a TPO-dependent hematopoietic cell line and of Mpl
and STAT3 in primary murine MK. Moreover, IFN- induces SOCS-1
production in these cells, which has been shown to inhibit TPO-induced
cell growth. Because SOCS protein expression is induced by many
cytokines and has been reported to extinguish signaling from several
hematopoietic cytokine receptors, these results identify a molecular
mechanism responsible for cytokine receptor cross-talk.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. M. Zimmerer, G. B. Lesinski, S. V. Kondadasula, V. I. Karpa, A. Lehman, A. RayChaudhury, B. Becknell, and W. E. Carson III
IFN-{alpha}-Induced Signal Transduction, Gene Expression, and Antitumor Activity of Immune Effector Cells Are Negatively Regulated by Suppressor of Cytokine Signaling Proteins
J. Immunol.,
April 15, 2007;
178(8):
4832 - 4845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Matuskova, A. K. Chauhan, B. Cambien, S. Astrof, V. S. Dole, C. L. Piffath, R. O. Hynes, and D. D. Wagner
Decreased Plasma Fibronectin Leads to Delayed Thrombus Growth in Injured Arterioles
Arterioscler. Thromb. Vasc. Biol.,
June 1, 2006;
26(6):
1391 - 1396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M Schmid, A Kreil, W Jessner, M Homoncik, C Datz, A Gangl, P Ferenci, and M Peck-Radosavljevic
Suppression of haematopoiesis during therapy of chronic hepatitis C with different interferon {alpha} mono and combination therapy regimens
Gut,
July 1, 2005;
54(7):
1014 - 1020.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Eriksen, V. H. Sommer, A. Woetmann, A. B. Rasmussen, C. Brender, A. Svejgaard, S. Skov, C. Geisler, and N. Odum
Bi-phasic Effect of Interferon (IFN)-{alpha}: IFN-{alpha} UP- AND DOWN-REGULATES INTERLEUKIN-4 SIGNALING IN HUMAN T CELLS
J. Biol. Chem.,
January 2, 2004;
279(1):
169 - 176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Linden and K. Kaushansky
The Glycan Domain of Thrombopoietin (TPO) Acts in trans to Enhance Secretion of the Hormone and Other Cytokines
J. Biol. Chem.,
September 13, 2002;
277(38):
35240 - 35247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Chacko and M. L. Adamo
Double-Stranded RNA Decreases IGF-I Gene Expression in a Protein Kinase R-Dependent, but Type I Interferon-Independent, Mechanism in C6 Rat Glioma Cells
Endocrinology,
February 1, 2002;
143(2):
525 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bousquet, V. Chesnokova, A. Kariagina, A. Ferrand, and S. Melmed
cAMP Neuropeptide Agonists Induce Pituitary Suppressor of Cytokine Signaling-3: Novel Negative Feedback Mechanism for Corticotroph Cytokine Action
Mol. Endocrinol.,
November 1, 2001;
15(11):
1880 - 1890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Greenhalgh and D. J. Hilton
Negative regulation of cytokine signaling
J. Leukoc. Biol.,
September 1, 2001;
70(3):
348 - 356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Lian, L. Wang, S. Yamaga, W. Bonds, Y. Beazer-Barclay, Y. Kluger, M. Gerstein, P. E. Newburger, N. Berliner, and S. M. Weissman
Genomic and proteomic analysis of the myeloid differentiation program
Blood,
August 1, 2001;
98(3):
513 - 524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Wang, E. Zorn, and J. Ritz
Specific down-regulation of interleukin-12 signaling through induction of phospho-STAT4 protein degradation
Blood,
June 15, 2001;
97(12):
3860 - 3866.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
