Essential role of GATA transcriptional factors in the activation of mast cells.
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 Cbeta were defective in these cells. These results identify that GATA has a critical role in the activation of mast cell.
Masuda
Akio
A
Division of Neurogenetics and Bioinformatics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan. amasuda@med.nagoya-u.ac.jp
Hashimoto
Katsunori
K
Yokoi
Toyoharu
T
Doi
Takeshi
T
Kodama
Tatsuhiko
T
Kume
Hiroaki
H
Ohno
Kinji
K
Matsuguchi
Tetsuya
T
D000107:Acetylation; D000818:Animals; D015550:Cell Degranulation; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D050989:GATA2 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D007073:Immunoglobulin E / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D006657:Histones; D034741:RNA, Small Interfering; D017455:Receptors, IgE; D007073:Immunoglobulin E