| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Neurogenetics and Bioinformatics, Center for Neurological Diseases and Cancer, and
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan;
Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan;
Tokyo New Drug Research Laboratories II, Kowa Company, Tokyo, Japan;
¶ Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan; and
|| Division of Biochemistry and Molecular Dentistry, Department of Developmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Mast cells are pivotal effector cells in IgE-mediated allergic reactions. GATA transcriptional factors such as GATA-1 and GATA-2 are expressed in mast cells, and recent studies have revealed that both GATA-1 and GATA-2 are required for mast cell development. However, the role of GATA transcriptional factors in differentiated mast cells has remained largely unknown. In this study, we repressed the activity of GATA-1 and GATA-2 by using three different approaches (inducible overexpression of a dominant-negative form of GATA, pharmacological inactivation, or small interfering RNA technology), and analyzed the molecular mechanisms of GATA transcriptional factors in the activation of mast cells. Surprisingly, the repression of GATA activity in differentiated mast cells led to the impairment of cell survival, IgE-induced degranulation, and cytokine production. Signal transduction and histone modification in the chromatin related to protein kinase C
were defective in these cells. These results identify that GATA has a critical role in the activation of mast cell.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the Japanese Society for the Promotion of Science and the Japanese Allergy Foundation, the Kao Foundation for Arts and Sciences, and the ONO Medical Research Foundation.
2 Address correspondence and reprint requests to Dr. Akio Masuda, Division of Neurogenetics and Bioinformatics, Center for Neural Disease and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail address: amasuda{at}med.nagoya-u.ac.jp
3 Abbreviations used in this paper: PKC, protein kinase C; SCF, stem cell factor; DNP, dinitrophenol; HSA, human serum albumin; BMMC, bone marrow-derived mast cell; DN, dominant negative; siRNA, small-interfering RNA; Dox, doxycycline; ChIP, chromatin immunoprecipitation; PCA, passive cutaneous anaphylaxis; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium.
This article has been cited by other articles:
|
|
 |
|
  D. Metcalf, I. Majewski, S. Mifsud, L. Di Rago, and W. S. Alexander Clonogenic mast cell progenitors and their excess numbers in chimeric BALB/c mice with inactivated GATA-1 PNAS, November 20, 2007; 104(47): 18642 - 18647. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
