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*
Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Melbourne, Australia;
Department of Pathology, Faculty of Medicine and Faculty of Dentistry, University of Toronto and Women’s College Hospital, Toronto, Ontario, Canada; and
F. Douglas Stephens Surgical Research Unit, Royal Children’s Hospital Research Foundation, Melbourne, Australia
Ets-1 is a transcription factor with restricted expression in
lymphocytes, and it has been implicated in the regulation of T cell
genes such as TCR
, TCRß, CD4, IL-2, and TNF-. We show in this
study that Ets-1 is also expressed in some mast cells constitutively
and can be induced in primary mast cells with stimuli that activate
mast cells. We also show that Ets-1 plays a role in the regulation of
granulocyte-macrophage CSF (GM-CSF), a cytokine expressed by activated
mast cells. We have characterized a murine growth factor-independent
mast cell line, FMP6-, derived from a factor-dependent cell
line, FMP1.6. FMP6- has acquired a distinct connective tissue mast
cell-like phenotype, as characterized by the expression of mast cell
proteases MMCP-4 and MMCP-6, expression of IL-12, and the
down-regulation of IL-4. The parental FMP1.6 cell line displays a
mucosal mast cell-like phenotype. FMP6- cells have increased Ets-1
expression and achieve growth-factor independence by the autocrine
production of GM-CSF and IL-3. Transient transfection of an Ets-1
expression construct in FMP6- cells results in transactivation of a
GM-CSF reporter, while a point mutation in the consensus Ets binding
site in the conserved lymphokine element, CLE0, abolishes Ets-1
transactivation. Importantly, antisense Ets-1 demonstrates an ability
to repress the activity of the GM-CSF reporter. These data suggest a
role for Ets-1 in mast cell growth regulation and activation, and
because of the central role of mast cells in inflammatory processes,
such as asthma and rheumatoid arthritis, they identify Ets-1 as
potentially contributing to the pathophysiology of such
diseases.
This article has been cited by other articles:
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H. Liu, M. Holm, X.-Q. Xie, M. Wolf-Watz, and T. Grundstrom AML1/Runx1 Recruits Calcineurin to Regulate Granulocyte Macrophage Colony-stimulating Factor by Ets1 Activation J. Biol. Chem., July 9, 2004; 279(28): 29398 - 29408. [Abstract] [Full Text] [PDF]
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 Y. Nakamura, S. Esnault, T. Maeda, E. A. B. Kelly, J. S. Malter, and N. N. Jarjour Ets-1 Regulates TNF-{alpha}-Induced Matrix Metalloproteinase-9 and Tenascin Expression in Primary Bronchial Fibroblasts J. Immunol., February 1, 2004; 172(3): 1945 - 1952. [Abstract] [Full Text] [PDF]
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 H. Liu and T. Grundstrom Calcium Regulation of GM-CSF by Calmodulin-Dependent Kinase II Phosphorylation of Ets1 Mol. Biol. Cell, December 1, 2002; 13(12): 4497 - 4507. [Abstract] [Full Text] [PDF]
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 S. Fujiie, K. Hieshima, D. Izawa, T. Nakayama, R. Fujisawa, H. Ohyanagi, and O. Yoshie Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3{alpha}/CCL20 in mucosal epithelial cells through NF-{kappa}B Int. Immunol., October 1, 2001; 13(10): 1255 - 1263. [Abstract] [Full Text] [PDF]
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