| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 14, 10212-10217, April 7, 2000
From the Department of Pathology, Yale School of Medicine, New
Haven, Connecticut 06520-8023
Interleukin-4 (IL-4) activates Stat6 (signal
transducer and activator of transcription 6) and plays multiple roles
in regulation of the immune system. IL-4 also triggers phosphorylation
of insulin receptor substrate (IRS), leading to stimulation of cell
growth. Moreover, IL-4 inhibits proliferation of a variety of cells,
but the molecular mechanism of its growth inhibitory effect is not understood. In this study, we demonstrated that IL-4 inhibited cell
growth of colon carcinoma cell lines (HT29 and WiDr) but promoted cell
growth of Burkitt's lymphoma cell lines (BL30 and BL41) in a
dose-dependent manner. The growth inhibition was not dependent on Stat6 activation, because Stat6 was activated at similar
levels in all cell lines in response to IL-4. Strikingly, IL-4
activated Stat1 in colon carcinoma cell lines but not in Burkitt's
lymphoma cell lines. Therefore, these results suggest that IL-4 induced
Stat1 activation, resulting in growth inhibition of colon carcinoma
cell lines. Importantly, we present evidence that Stat1 is necessary
for IL-4-mediated growth inhibition using Stat1-deficient and
Stat1-reconstituted cells. The growth inhibitory effect of IL-4 was
diminished in Stat1-deficient cells, whereas it was restored in
Stat1-reconstituted cells. In addition, the expression of
dominant-negative Stat1 in HT29 cells led to the loss of growth
inhibition in response to IL-4. Taken together, our data suggest that
IL-4 activates Stat1, leading to cell growth inhibition in colon cancer
cells. Thus, this study demonstrates, for the first time, a molecular
mechanism by which IL-4 inhibits cell growth.
Interleukin-4 Mediates Cell Growth Inhibition through
Activation of Stat1*
*
This work was supported by grants from the National
Institutes of Health (RO1GM55590 and RO1AI34522 to X. Y. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
A recipient of a Career Development Award (KO4AE01356) from the
National Institutes of Health. To whom correspondence should be
addressed. Tel.: 203-737-1246; Fax: 203-737-1247; E-mail:
xin-yuan.fu@yale.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C.-R. Yu, R. M. Mahdi, S. Ebong, B. P. Vistica, J. Chen, Y. Guo, I. Gery, and C. E. Egwuagu Cell Proliferation and STAT6 Pathways Are Negatively Regulated in T Cells by STAT1 and Suppressors of Cytokine Signaling J. Immunol., July 15, 2004; 173(2): 737 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I.-S. Lean, S. A. C. McDonald, M. Bajaj-Elliott, R. C. G. Pollok, M. J. G. Farthing, and V. McDonald Interleukin-4 and Transforming Growth Factor {beta} Have Opposing Regulatory Effects on Gamma Interferon-Mediated Inhibition of Cryptosporidium parvum Reproduction Infect. Immun., August 1, 2003; 71(8): 4580 - 4585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. W. Lee, B. Hennig, and M. Toborek Redox-regulated mechanisms of IL-4-induced MCP-1 expression in human vascular endothelial cells Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H185 - H192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L.-Y. Chang, A. Mosoian, R. Pine, M. E. Klotman, and J. P. Moore A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation J. Virol., January 15, 2002; 76(2): 569 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Shureiqi and S. M. Lippman Lipoxygenase Modulation to Reverse Carcinogenesis Cancer Res., September 1, 2001; 61(17): 6307 - 6312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shureiqi, X. Xu, D. Chen, R. Lotan, J. S. Morris, S. M. Fischer, and S. M. Lippman Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Esophageal Cancer Cells by Restoring 15-Lipoxygenase-1 Expression Cancer Res., June 1, 2001; 61(12): 4879 - 4884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shureiqi, D. Chen, R. Lotan, P. Yang, R. A. Newman, S. M. Fischer, and S. M. Lippman 15-Lipoxygenase-1 Mediates Nonsteroidal Anti-Inflammatory Drug-induced Apoptosis Independently of Cyclooxygenase-2 in Colon Cancer Cells Cancer Res., December 1, 2000; 60(24): 6846 - 6850. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
