Essential Role of GATA Transcriptional Factors in the Activation of Mast Cells1

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 Cβ were defective in these cells. These results identify that GATA has a critical role in the activation of mast cell.

[1]  D. Chi,et al.  The human mast cell: an overview. , 2006, Methods in molecular biology.

[2]  E. Gelfand,et al.  Protein kinase C α, βI, and βII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways , 2005 .

[3]  Kirby D. Johnson,et al.  Developmental control via GATA factor interplay at chromatin domains , 2005, Journal of cellular physiology.

[4]  M. Nishiyama,et al.  GATA-1 is required for expression of Fc{epsilon}RI on mast cells: analysis of mast cells derived from GATA-1 knockdown mouse bone marrow. , 2005, International immunology.

[5]  M. Beaven,et al.  An Essential Role for Phospholipase D in the Activation of Protein Kinase C and Degranulation in Mast Cells , 2005, The Journal of Immunology.

[6]  Mildred Kwan,et al.  An intron GATA‐binding site regulates chromatin accessibility and is essential for IL‐4 gene expression in mast cells , 2005, European journal of immunology.

[7]  Masayuki Yamamoto,et al.  Gene expression regulation and domain function of hematopoietic GATA factors. , 2005, Seminars in cell & developmental biology.

[8]  D. Rawlings,et al.  Protein Kinase C βII Regulates Akt Phosphorylation on Ser-473 in a Cell Type- and Stimulus-specific Fashion*♦ , 2004, Journal of Biological Chemistry.

[9]  A. Masuda,et al.  The Interaction between GATA Proteins and Activator Protein-1 Promotes the Transcription of IL-13 in Mast Cells1 , 2004, The Journal of Immunology.

[10]  P. Tolar,et al.  Positive and negative regulation of Fcϵ receptor I‐mediated signaling events by Lyn kinase C‐terminal tyrosine phosphorylation , 2004 .

[11]  T. Zuberbier,et al.  The transcription factor profile of human mast cells in comparison with monocytes and granulocytes , 2004, Cellular and Molecular Life Sciences CMLS.

[12]  G. Blobel,et al.  Formation of a Tissue-Specific Histone Acetylation Pattern by the Hematopoietic Transcription Factor GATA-1 , 2003, Molecular and Cellular Biology.

[13]  S. Orkin,et al.  GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant , 2003, The Journal of experimental medicine.

[14]  M. Nishiyama,et al.  Regulation of Cell Type-Specific Mouse FcεRI β-Chain Gene Expression by GATA-1 Via Four GATA Motifs in the Promoter1 , 2003, The Journal of Immunology.

[15]  John Anastasi,et al.  Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates. , 2002, Immunity.

[16]  A. Masuda,et al.  Th2 Cytokine Production from Mast Cells Is Directly Induced by Lipopolysaccharide and Distinctly Regulated by c-Jun N-Terminal Kinase and p38 Pathways1 , 2002, The Journal of Immunology.

[17]  A. Bird,et al.  Gene silencing quantitatively controls the function of a developmental trans-activator. , 2002, Molecular cell.

[18]  G. Nilsson,et al.  Essential Role of the Prosurvival bcl-2 Homologue A1 in Mast Cell Survival After Allergic Activation , 2001, The Journal of experimental medicine.

[19]  A. Masuda,et al.  Interleukin-15 Prevents Mouse Mast Cell Apoptosis through STAT6-mediated Bcl-xL Expression* , 2001, The Journal of Biological Chemistry.

[20]  B. Baird,et al.  Activated Cdc42/Rac reconstitutes FcɛRI-mediated Ca2+ mobilization and degranulation in mutant RBL mast cells , 2001 .

[21]  A. Masuda,et al.  Cutting Edge: Naturally Occurring Soluble Form of Mouse Toll-Like Receptor 4 Inhibits Lipopolysaccharide Signaling1 , 2000, The Journal of Immunology.

[22]  J. Molkentin.  The Zinc Finger-containing Transcription Factors GATA-4, -5, and -6 , 2000, The Journal of Biological Chemistry.

[23]  J. Wedemeyer,et al.  Roles of mast cells and basophils in innate and acquired immunity. , 2000, Current opinion in immunology.

[24]  M. Kubo,et al.  Interleukin-15 Induces Rapid Tyrosine Phosphorylation of STAT6 and the Expression of Interleukin-4 in Mouse Mast Cells* , 2000, The Journal of Biological Chemistry.

[25]  T. Kawakami,et al.  Akt-Dependent Cytokine Production in Mast Cells , 2000, Journal of Experimental Medicine.

[26]  S. Hartman,et al.  Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk and Syk. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  T. Kodama,et al.  A novel cell adhesion inhibitor, K-7174, reduces the endothelial VCAM-1 induction by inflammatory cytokines, acting through the regulation of GATA. , 2000, Biochemical and biophysical research communications.

[28]  M. Leitges,et al.  Inhibition of degranulation and interleukin-6 production in mast cells derived from mice deficient in protein kinase Cbeta. , 2000, Blood.

[29]  J. D. Engel,et al.  GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies. , 2000, Blood.

[30]  C. Ra,et al.  The transcription factors Elf-1 and GATA-1 bind to cell-specific enhancer elements of human high-affinity IgE receptor alpha-chain gene. , 1999, Journal of immunology.

[31]  R. Sagi-Eisenberg,et al.  Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells , 1999, The Journal of experimental medicine.

[32]  Satoru Takahashi,et al.  Differential roles of GATA‐1 and GATA‐2 in growth and differentiation of mast cells , 1998, Genes to cells : devoted to molecular & cellular mechanisms.

[33]  S. Orkin,et al.  Embryonic stem cells and transgenic mice in the study of hematopoiesis. , 1998, The International journal of developmental biology.

[34]  S. Orkin,et al.  Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. , 1997, Blood.

[35]  Y. Kitamura,et al.  Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: demonstration by in situ hybridization. , 1996, Blood.

[36]  G. Blobe,et al.  Selective regulation of expression of protein kinase C beta isoenzymes occurs via alternative splicing. , 1993, The Journal of biological chemistry.

[37]  K. Suzuki,et al.  Positive and negative regulation of the transcription of the human protein kinase C beta gene. , 1992, The Journal of biological chemistry.

[38]  L. Zon,et al.  GATA-binding transcription factors in mast cells regulate the promoter of the mast cell carboxypeptidase A gene. , 1991, The Journal of biological chemistry.

[39]  M. Tsai,et al.  The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype , 1991, The Journal of experimental medicine.