|
|
Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-05-1521.
 Previous Article | Table of Contents | Next Article 
Blood, 1 April 2003, Vol. 101, No. 7, pp. 2727-2735
IMMUNOBIOLOGY
Type I interferon differential therapy for erythroleukemia:
specificity of STAT activation
Vanessa S. Cull,
Peta A. Tilbrook,
Emmalene J. Bartlett,
Natalie L. Brekalo, and
Cassandra M. James
From the Division of Veterinary and Biomedical
Sciences, Western Australian Biomedical Research Institute, Murdoch
University, Perth; and Laboratory for Cancer Medicine, Western
Australian Institute for Medical Research, Royal Perth Hospital, Centre
for Medical Research, The University of Western Australia, Perth,
Western Australia, Australia.
Type I interferons (IFNs), pleiotropic cytokines with antiviral,
antiproliferative, apoptotic, and immunoregulatory functions, are
efficacious in the treatment of malignancies, viral infections, and
autoimmune diseases. Binding of these cytokines to their cognate receptor leads to activation of the Jak-signal transducers and activators of transcription (STAT) signaling pathway and
altered gene expression. This signal pathway has been intensely studied using human IFN- 2 and IFN- . However, there are over 14 human IFN- subtypes and over 10 murine IFN- subtypes, with a single IFN- subtype in both species. J2E cells are immortalized at the proerythroblast stage of development and produce a rapid and fatal erythroleukemia in vivo. These cells retain the ability to
respond to erythropoietin in vitro by proliferating, differentiating, and remaining viable in the absence of serum. Here, we show that J2E
cells are also functionally regulated differentially by IFN subtype
treatment in vitro. A novel finding was the selective activation of
STAT and mitogen-activated protein kinase (MAPK) molecules by different subtypes binding the IFN receptor. These findings indicate distinct effects for individual type I IFN subtypes, which are able to differentially activate members of the STAT and MAPK
family. Finally, we investigated the efficacy of IFN naked
DNA therapy in treating J2E-induced erythroleukemia in athymic nude
mice. IFN subtypes differentially regulated the onset of erythroleukemia with delayed onset and increased survival, possibly via
a reduction in cell viability, and enhanced antiproliferative and
apoptotic effects observed for IFNA6 and IFNA9
treatment, respectively. Moreover, these data highlight the
necessity to choose the best IFN subtype in disease treatment.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Nociari, O. Ocheretina, M. Murphy, and E. Falck-Pedersen
Adenovirus Induction of IRF3 Occurs through a Binary Trigger Targeting Jun N-Terminal Kinase and TBK1 Kinase Cascades and Type I Interferon Autocrine Signaling
J. Virol.,
May 1, 2009;
83(9):
4081 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. van Pesch, H. Lanaya, J.-C. Renauld, and T. Michiels
Characterization of the Murine Alpha Interferon Gene Family
J. Virol.,
August 1, 2004;
78(15):
8219 - 8228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Y. Kim, E. J. Park, E.-h. Joe, and I. Jou
Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia
J. Immunol.,
December 1, 2003;
171(11):
6072 - 6079.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. U. Hilkens, J. F. Schlaak, and I. M. Kerr
Differential Responses to IFN-{alpha} Subtypes in Human T Cells and Dendritic Cells
J. Immunol.,
November 15, 2003;
171(10):
5255 - 5263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
