title: The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells.
abstract: FcεRI, which is composed of α, β, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-β1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-β1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family transcriptional factors, is upregulated by TGF-β/Smad signaling in mouse bone marrow-derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed the transcription of genes encoding FcεRIα, FcεRIβ, and c-Kit, resulting in a reduction in cell surface FcεRI and c-Kit expression. Additionally, forced expression of Ehf suppressed FcεRI-mediated degranulation and cytokine production. Ehf inhibited the promoter activity of genes encoding FcεRIα, FcεRIβ, and c-Kit by binding to these gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1 and GATA-2 are positive regulators of FcεRI and c-Kit expression, decreased expression of GATAs may be also involved in the reduction of FcεRI and c-Kit expression. Decreased expression of Stat5 may contribute to the suppression of cytokine production by BMMCs. In part, mast cell response to TGF-β1 was mimicked by forced expression of Ehf, suggesting that TGF-β1 suppresses FcεRI and c-Kit expression and suppresses FcεRI-mediated activation through upregulation of Ehf.
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; and.
authors: Susumu
authors: S
authors: Yamazaki
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; nbnakano@juntendo.ac.jp.
authors: Nobuhiro
authors: N
authors: Nakano
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; and.
authors: Asuka
authors: A
authors: Honjo
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
authors: Mutsuko
authors: M
authors: Hara
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
authors: Keiko
authors: K
authors: Maeda
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Tokyo 125-8585, Japan.
authors: Chiharu
authors: C
authors: Nishiyama
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
authors: Jiro
authors: J
authors: Kitaura
authors: Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; and.
authors: Yoshikazu
authors: Y
authors: Ohtsuka
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
authors: Ko
authors: K
authors: Okumura
authors: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan;
authors: Hideoki
authors: H
authors: Ogawa
authors: Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; and.
authors: Toshiaki
authors: T
authors: Shimizu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D015550:Cell Degranulation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; C112442:Ehf protein, mouse; C521907:Fc-epsilon receptor I beta-chain, mouse; C579617:FcepsilonRIalpha protein, mouse; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017455:Receptors, IgE; D050799:STAT5 Transcription Factor; D051785:Smad Proteins; C494096:Stat5b protein, mouse; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D007073:Immunoglobulin E; D019009:Proto-Oncogene Proteins c-kit