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A key role for ATF3 in regulating mast cell survival and mediator release.
Title | A key role for ATF3 in regulating mast cell survival and mediator release. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Gilchrist, M, Henderson, WR, Morotti, A, Johnson, CD, Nachman, A, Schmitz, F, Smith, KD, Aderem, A |
Journal | Blood |
Volume | 115 |
Issue | 23 |
Pagination | 4734-41 |
Date Published | 2010 Jun 10 |
ISSN | 1528-0020 |
Keywords | Activating Transcription Factor 3, Animals, Apoptosis, bcl-Associated Death Protein, Bone Marrow Cells, Cell Survival, Gene Expression Regulation, Hypersensitivity, Inflammation, Inflammation Mediators, Interleukin-3, Interleukin-4, Interleukin-6, Mast Cells, Mice, Mice, Knockout, Phosphorylation, Receptors, IgE, Signal Transduction |
Abstract | Activating transcription factor 3 (ATF3) is a basic leucine zipper transcription factor that plays a regulatory role in inflammation, cell division, and apoptosis. Mast cells (MCs) initiate many inflammatory responses and have a central role in allergy and allergic diseases. We report here that ATF3 has a central role in MC development and function. Bone marrow-derived MC populations from ATF3-deficient mice are unresponsive to interleukin-3 (IL-3)-induced maturation signals, and this correlates with increased apoptosis, diminished activation of the Akt kinase, and decreased phosphorylation of the proapoptotic protein Bad. Furthermore, ATF3-null mice lacked MCs in the peritoneum and dermis, showing that the in vitro results are recapitulated in vivo. ATF3-null MCs also showed functional defects; high-affinity immunoglobulin E receptor-mediated degranulation was significantly inhibited, whereas IL-4 and IL-6 expression was enhanced. This dual role of ATF3 provides insight into the complex interplay between MC development and its subsequent physiologic role. |
DOI | 10.1182/blood-2009-03-213512 |
Alternate Journal | Blood |
PubMed ID | 20203264 |