17 results on '"Shimokawa, Toshibumi"'
Search Results
2. Genetic variants of the IgA Fc receptor (FcαR, CD89) promoter in chronic hepatitis C patients
- Author
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Watanabe, Azuma, Shimokawa, Toshibumi, Moriyama, Mitsuhiko, Komine, Fumihiko, Amaki, Shuichi, Arakawa, Yasuyuki, and Ra, Chisei
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- 2006
- Full Text
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3. Regulation of nephrin gene by the Ets transcription factor, GA-binding protein
- Author
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Ristola, Mervi, Arpiainen, Satu, Shimokawa, Toshibumi, Ra, Chisei, Tienari, Jukka, Saleem, Moin A., Holthöfer, Harry, and Lehtonen, Sanna
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- 2013
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4. Polymorphism in promoter region of Fcα receptor gene in patients with IgA nephropathy
- Author
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Tsuge, Toshinao, Shimokawa, Toshibumi, Horikoshi, Satoshi, Tomino, Yasuhiko, and Ra, Chisei
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- 2001
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5. Identification and characterization of the promoter for the gene encoding the human myeloid IgA Fc receptor (FcαR, CD89)
- Author
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Shimokawa, Toshibumi, Tsuge, Toshinao, Okumura, Ko, and Ra, Chisei
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- 2000
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6. High affinity receptor for IgE stimulation activates protein kinase D augmenting activator protein-1 activity for cytokine producing in mast cells
- Author
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Yamashita, Kyoko, Gon, Yasuhiro, Shimokawa, Toshibumi, Nunomura, Satoshi, Endo, Daisuke, Miyata, Naoko, Hashimoto, Shu, Van Lint, Johan, and Ra, Chisei
- Published
- 2010
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7. Identification of the C/EBPα C-terminal tail residues involved in the protein interaction with GABP and their potency in myeloid differentiation of K562 cells.
- Author
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Shimokawa, Toshibumi, Nunomura, Satoshi, Fujisawa, Daisuke, and Ra, Chisei
- Abstract
Abstract: The CCAAT/enhancer-binding protein α (C/EBPα) is the member of a family of related basic leucine zipper (bZIP) transcription factors and is critical for granulopoiesis. We previously demonstrated that C/EBPα interacts with the ETS domain of widely expressed GABPα, which leads to cooperative transcriptional activation of the myeloid-specific promoter for human FCAR encoding the Fc receptor for IgA (FcαR, CD89) in part by facilitating recruitment of C/EBPα to the promoter. The C/EBPα molecule contains transactivation domains (TADs) at its N-terminus and a DNA-binding and dimerization bZIP structure at its C-terminus. We demonstrate here that GABPα interacts with the last 18 residues of the C/EBPα C-terminus beyond the bZIP DNA-binding and dimerizing region. Deletion of this C-terminus resulted in loss of GABPα interaction but not affecting its DNA binding ability, indicating that it is not required for homodimer formation. Moreover, the C-terminus confers the ability to functionally synergize with GABP on a heterologous TAD when fused to the C-terminus of the VP16 TAD. We identified a three-amino acid stretch (amino acids 341–343) that is important for both functional and protein interactions with GABP. Ectopic expression in K562 cells of C/EBPα mutant incapable of interacting with GABPα does not induce expression of granulocytic differentiation markers including CD15, CD11b, GCSF-R and C/EBPε, and does not inhibit proliferation, whereas wild type does. These results demonstrate the functional importance of the C/EBPα C-terminus beyond the bZIP DNA-binding and dimerization region, which may mediate cooperative activation by C/EBPα and GABP of myeloid-specific genes involved in C/EBPα-dependent granulopoiesis. [Copyright &y& Elsevier]
- Published
- 2013
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8. Alternative splicing of myeloid IgA Fc receptor (FcαR, CD89) transcripts in inflammatory responses
- Author
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Togo, Shinsaku, Shimokawa, Toshibumi, Fukuchi, Yoshinosuke, and Ra, Chisei
- Subjects
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IMMUNOGLOBULINS , *INTERLEUKINS , *TRANSFORMING growth factors - Abstract
More than 10 splice variants of the Fc receptor for IgA (FcαR, CD89) have been identified in human myeloid cells. In this study, we quantified FcαR splice transcripts ΔEC2 and Δ66EC2, which lack the entire and a part of the homologous immunoglobulin-like extracellular domain 2 (EC2), respectively. Tumor necrosis factor-α was found to specifically increase the ratio of ΔEC2 to the wild type CD89 in neutrophils and conversely decrease the ΔEC2 ratio in monocytes. We also observed a significant decrease in the neutrophil ΔEC2/CD89 ratio in pneumonia patients. These results suggest that ΔEC2 is differentially regulated and could be involved in immunoregulation of IgA-mediated host defense. [Copyright &y& Elsevier]
- Published
- 2003
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9. FcεRI-induced mast cell cytokine production critically involves an aspartic acid residue (D234) in the C-terminal intracellular domain of the FcεRIβ chain
- Author
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Terada, Tomoyoshi, Nunomura, Satoshi, Shimokawa, Toshibumi, Murayama, Koichi, Era, Seiichi, Kondo, Naomi, and Ra, Chisei
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MAST cells , *IMMUNOGLOBULIN E , *CYTOKINES , *ASPARTIC acid , *CIRCULAR dichroism , *CYTOPLASM , *MUTAGENESIS - Abstract
Abstract: The high affinity IgE Fc receptor (FcεRI) β chain is well implicated as a signal amplifier through the immunoreceptor tyrosine-based activation motif (ITAM) in its C-terminal intracellular region. Our previous study, however, demonstrated that mutation in all of the three tyrosine residues within the FcεRIβ ITAM did not impair FcεRI-induced cytokine production, suggesting a possible functional region other than the ITAM. To investigate the ITAM-independent mechanism by which FcεRIβ regulates FcεRI-induced cytokine production, mouse mast cells expressing various FcεRIβ mutants were generated. We observed that truncation of the FcεRIβ C-terminus downstream of the ITAM resulted in a considerable decrease in FcεRI-induced IL-6 production but not degranulation. Furthermore, mutagenesis of a single C-terminal aspartic acid (D234) to alanine (β-D234A) also significantly impaired IL-6 production. In addition, the similarity between the circular dichroism (CD) spectra of the wild type and β-D234A suggests that the secondary structure of the FcεRIβ C-terminus was not affected by the D234A mutation. Consistently, we did not observe any effect of this mutation on FcεRI-induced tyrosine phosphorylation of FcεRIβ. These observations strongly suggest a novel signaling pathway mediated by the cytoplasmic tail downstream of the FcεRIβ ITAM. [Copyright &y& Elsevier]
- Published
- 2011
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10. Functionality of the IgA Fc receptor (FcαR, CD89) is down-regulated by extensive engagement of FcɛRI
- Author
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Matsui, Takashi, Nunomura, Satoshi, Shimokawa, Toshibumi, Yoshimaru, Tetsuro, and Ra, Chisei
- Subjects
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MAST cells , *CYTOSKELETON , *IMMUNOGLOBULIN A , *BASOPHILS , *NEUTROPHILS , *ALLERGIES , *LEUKEMIA , *CELL lines , *PATIENTS - Abstract
Abstract: Besides mast cells and basophils, the high-affinity IgE Fc receptor (FcɛRI) is exclusively expressed on certain FcαR (IgA Fc receptor)-expressing immune cells such as neutrophils in allergic patients. Transfected rat basophilic leukemia cell line (RBL-2H3) co-expressing FcɛRI and FcαR was analyzed for effects of simultaneous receptor engagement by their specific antibodies on degranulation and signaling. Whereas supraoptimal FcɛRI engagement decreased degranulation, which is known as a bell-shaped dose–response curve, such inhibitory effect was not observed with FcαR engagement. However, simultaneous engagement of FcɛRI and FcαR showed that supraoptimal FcɛRI engagement down-regulates FcαR-mediated degranulation. This inhibition was associated with extensive phosphorylation of inositol polyphosphate 5′-phosphatase SHIP1 and FcɛRIβ, and reversed by adding actin-depolymerizing drug, latrunculin B. The results suggest an endogenous mechanism by which FcαR functionality is down-regulated in an ‘allergic environment’ where FcɛRI is co-expressed and extensively cross-linked on FcαR-expressing effector cells. [Copyright &y& Elsevier]
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- 2008
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11. Cooperative Regulation of Fc Receptor γ-Chain Gene Expression by Multiple Transcription Factors, Including Spi, GABP, and Elf-1.
- Author
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Takahashi, Kyoko, Hayashi, Natsuko, Shimokawa, Toshibumi, Umehara, Nagayoshi, Kaminogawa, Shuichi, and Ra, Chisei
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FC receptors , *CELL receptors , *RNA , *CHROMATIN , *GENE expression - Abstract
The Fc receptor γ-chain (FcRγ), which was first identified as a constituent of the high affinity IgE receptor, associates with various cell surface receptors to mediate intracellular signals. We identified three transcriptional enhancer elements in the 5′ region of the human FcRγ gene; one of the cis-elements was recognized by the transcription factor Sp-1 and another was recognized by GABP or Elf-1. The sequence of the other element was similar to a binding motif of the C/EBP family. Overexpression experiments showed that these transcription factors cooperatively activated the FcRγ promoter. Furthermore, inactivation of the GABP-binding site by nucleotide substitutions as well as repression of GABPα expression by RNA interference reduced Sp1-mediated transactivation of the FcRγ promoter, demonstrating that Sp1 and GABP synergistically activated the FcRγ promoter. This synergistic activation was suggested to require physical interaction between the two transcription factors, because the Ets domain of GABPγ was demonstrated to directly bind Sp1. On the other hand, GABP and Elf-1, whose recognition sequences overlapped, were shown to bind the FcRγ gene with similar affinity in the context of chromatin, although Elf-1 exerted weaker enhancer activity for FcRγ gene expression than did GABP. Both were thought to compete for binding to the element, because additional expression of Elf-1 in combination with Sp1 and GABP reduced FcRγ promoter activity. Such functional and physical interactions among transcription factors involved in the cooperative regulation of FcRγ gene expression as revealed in this study will become promising targets for medical applications against various immune diseases involving FcRγ. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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12. Identification of the C/EBPα C-terminal tail residues involved in the protein interaction with GABP and their potency in myeloid differentiation of K562 cells.
- Author
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Shimokawa T, Nunomura S, Fujisawa D, and Ra C
- Subjects
- Base Sequence, CCAAT-Enhancer-Binding Protein-alpha chemistry, CCAAT-Enhancer-Binding Protein-alpha metabolism, DNA Primers, Electrophoretic Mobility Shift Assay, Humans, K562 Cells, Protein Binding, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-alpha physiology, Cell Differentiation physiology, GA-Binding Protein Transcription Factor metabolism
- Abstract
The CCAAT/enhancer-binding protein α (C/EBPα) is the member of a family of related basic leucine zipper (bZIP) transcription factors and is critical for granulopoiesis. We previously demonstrated that C/EBPα interacts with the ETS domain of widely expressed GABPα, which leads to cooperative transcriptional activation of the myeloid-specific promoter for human FCAR encoding the Fc receptor for IgA (FcαR, CD89) in part by facilitating recruitment of C/EBPα to the promoter. The C/EBPα molecule contains transactivation domains (TADs) at its N-terminus and a DNA-binding and dimerization bZIP structure at its C-terminus. We demonstrate here that GABPα interacts with the last 18 residues of the C/EBPα C-terminus beyond the bZIP DNA-binding and dimerizing region. Deletion of this C-terminus resulted in loss of GABPα interaction but not affecting its DNA binding ability, indicating that it is not required for homodimer formation. Moreover, the C-terminus confers the ability to functionally synergize with GABP on a heterologous TAD when fused to the C-terminus of the VP16 TAD. We identified a three-amino acid stretch (amino acids 341-343) that is important for both functional and protein interactions with GABP. Ectopic expression in K562 cells of C/EBPα mutant incapable of interacting with GABPα does not induce expression of granulocytic differentiation markers including CD15, CD11b, GCSF-R and C/EBPε, and does not inhibit proliferation, whereas wild type does. These results demonstrate the functional importance of the C/EBPα C-terminus beyond the bZIP DNA-binding and dimerization region, which may mediate cooperative activation by C/EBPα and GABP of myeloid-specific genes involved in C/EBPα-dependent granulopoiesis., (© 2013.)
- Published
- 2013
- Full Text
- View/download PDF
13. Development of pyrrole-imidazole polyamide targeting fc receptor common gamma chain for the treatment of immune-complex related renal disease.
- Author
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Kajiwara M, Ueno T, Fukuda N, Matsuda H, Shimokawa T, Kitai M, Tsunemi A, Fuke Y, Fujita T, Matsumoto K, Matsumoto Y, Ra C, and Soma M
- Subjects
- Animals, Cell Line, Cells, Cultured, Gene Expression Regulation drug effects, Immune Complex Diseases drug therapy, Kidney Diseases drug therapy, Leukocytes, Mononuclear, Male, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, RNA, Messenger metabolism, Imidazoles chemistry, Nylons pharmacology, Pyrroles chemistry, Receptors, IgG genetics
- Abstract
Fcγ receptors I and III are thought to be involved in the development of lupus nephritis. Expression of Fc receptor common gamma chain (FcRγ) is necessary for the stable expression of Fcγ receptors I and III. The aim of this study was to develop a novel agent for the treatment of immune complex related renal disease using a gene regulator, pyrrole(Py)-imidazole(Im) (PI) polyamide, targeting the mouse FcRγ gene promoter. Two PI polyamides targeting FcRγ promoters were designed and synthesized. The effect of the PI polyamides on FcRγ mRNA expression was evaluated in J774.A cells by real-time polymerase chain reaction (PCR), and CD16/32 protein expression was determined by immunocytochemical analysis and flow cytometry. The effects of these polyamides on FcRγ gene expression and CD16/32 protein expression were evaluated in mouse peripheral blood mononuclear cells (PBMCs). One milligram per kilogram body weight of PI polyamide was injected via the tail vein every 2 d for 1 week and PBMCs were collected and analyzed. PI polyamide showed a specific binding to the target DNA in a gel mobility shift assay. Treatment of J774.A cells with 1.0 µM PI polyamide 1 significantly reduced FcRγ mRNA expression and CD16/32 surface protein expression in J774.A cells. Similarly, PI polyamide significantly decreased expression of FcRγ mRNA and CD16/32 in the PBMCs of C57B6 mice. PI polyamide designed to bind the FcRγ promoter decreased FcRγ gene and CD16/32 protein expression. PI polyamide targeting the FcRγ gene may be a novel gene regulator for the prevention of lupus nephritis or other immune complex-related disease.
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- 2012
- Full Text
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14. Amino acid residues in the beta3 strand and subsequent loop of the conserved ETS domain that mediate basic leucine zipper (bZIP) recruitment and potentially distinguish functional attributes of Ets proteins.
- Author
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Shimokawa T, Nunomura S, Enomoto Y, and Ra C
- Subjects
- DNA metabolism, GA-Binding Protein Transcription Factor genetics, HeLa Cells, Humans, Mutation, Nuclear Proteins genetics, Promoter Regions, Genetic, Protein Interaction Mapping, Protein Structure, Secondary, Protein Structure, Tertiary, Proto-Oncogene Proteins c-ets genetics, Transcription Factors genetics, Transcriptional Activation, CCAAT-Enhancer-Binding Protein-alpha metabolism, GA-Binding Protein Transcription Factor metabolism, Leucine Zippers, Nuclear Proteins metabolism, Proto-Oncogene Proteins c-ets metabolism, Transcription Factors metabolism
- Abstract
Ets family members share a conserved DNA-binding ETS domain, and serve a variety of roles in development, differentiation and oncogenesis. Besides DNA binding, the ETS domain also participates in protein-protein interactions with other structurally unrelated transcription factors. Although this mechanism appears to confer tissue- or development stage-specific functions on individual Ets proteins, the biological significance of many of these interactions remains to be evaluated, because their molecular basis has been elusive. We previously demonstrated a direct interaction between the ETS domain of the widely expressed GABPalpha (GA-binding protein alpha) and the granulocyte inducer C/EBPalpha (CCAAT/enhancer-binding protein alpha), and suggested its involvement in co-operative transcriptional activation of myeloid-specific genes, such as human FCAR encoding FcalphaR [Fc receptor for IgA (CD89)]. By deletion analysis, we identified helix alpha3 and the beta3/beta4 region as the C/EBPalpha-interacting region. Domain-swapping of individual sub-domains with those of other Ets proteins allowed us to highlight beta-strand 3 and the subsequent loop, which when exchanged by those of Elf-1 (E74-like factor 1) reduced the ability to recruit C/EBPalpha. Further analysis identified a four-amino acid swap mutation of this region (I387L/C388A/K393Q/F395L) that reduces both physical interaction and co-operative transcriptional activation with C/EBPalpha without affecting its transactivation capacity by itself. Moreover, re-ChIP (re-chromatin immunoprecipitation) analysis demonstrated that GABPalpha recruits C/EBPalpha to the FCAR promoter, depending on these residues. The identified amino acid residues could confer the specificity of the action on the Ets proteins in diverse biological processes through mediating the recruitment of its partner factor.
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- 2010
- Full Text
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15. C/EBPalpha functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (Fc alphaR, CD89) gene promoter.
- Author
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Shimokawa T and Ra C
- Subjects
- Base Sequence, Binding Sites, CCAAT-Enhancer-Binding Protein-alpha chemistry, Cell Line, Cell Lineage, Chromatin Immunoprecipitation, DNA chemistry, Electrophoresis, Polyacrylamide Gel, Genes, Reporter, HeLa Cells, Humans, Jurkat Cells, Models, Genetic, Molecular Sequence Data, Plasmids metabolism, Protein Binding, Recombinant Fusion Proteins chemistry, Transcription, Genetic, Transcriptional Activation, Transfection, U937 Cells, Antigens, CD genetics, Antigens, CD metabolism, CCAAT-Enhancer-Binding Protein-alpha metabolism, Promoter Regions, Genetic, Receptors, Fc genetics, Receptors, Fc metabolism
- Abstract
Human Fcalpha receptor (Fc alphaR; CD89), the receptor for the crystallizable fragment (Fc) of immunoglobulin A (IgA), is expressed exclusively in myeloid cells, including granulocytes and monocytes/macrophages, and is considered to define a crucial role of these cells in immune and inflammatory responses. A 259-base pair fragment of the FCAR promoter is sufficient to direct myeloid expression of a reporter gene and contains functionally important binding sites for CCAAT/enhancer-binding protein alpha (C/EBPalpha) (CE1, CE2, and CE3) and an unidentified Ets-like nuclear protein. Here, we show that the Ets-binding site is bound by a heterodimer composed of GA-binding protein alpha (GABPalpha), an Ets-related factor, and GABPbeta, a Notch-related protein. Cotransfection of GABP increased FCAR promoter activity 3.7-fold through the Ets-binding site. GABP and C/EBPalpha synergistically activated the FCAR promoter 280-fold. Consistent with these observations, in vitro binding analyses revealed a physical interaction between the GABPalpha subunit and C/EBPalpha. This is the first report demonstrating both physical and functional interactions between GABP and C/EBPalpha and will provide new insights into the molecular basis of myeloid gene expression.
- Published
- 2005
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16. C/EBP alpha and Ets protein family members regulate the human myeloid IgA Fc receptor (Fc alpha R, CD89) promoter.
- Author
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Shimokawa T and Ra C
- Subjects
- 5' Untranslated Regions chemistry, 5' Untranslated Regions immunology, Amino Acid Motifs genetics, Amino Acid Motifs immunology, Base Sequence, Binding Sites genetics, Binding Sites immunology, CCAAT-Enhancer-Binding Protein-alpha genetics, CCAAT-Enhancer-Binding Protein-alpha metabolism, Codon, Initiator chemistry, Codon, Initiator immunology, DNA-Binding Proteins chemistry, DNA-Binding Proteins metabolism, Ephrin-A2 genetics, Ephrin-A2 metabolism, HeLa Cells, Humans, Jurkat Cells, Molecular Sequence Data, Multigene Family immunology, Protein Binding genetics, Protein Binding immunology, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-ets, Receptors, Fc antagonists & inhibitors, Trans-Activators genetics, Trans-Activators metabolism, Trans-Activators physiology, Transcription Factors genetics, Transcription Factors metabolism, Transcriptional Activation immunology, Tumor Cells, Cultured, U937 Cells, Antigens, CD genetics, Antigens, CD metabolism, CCAAT-Enhancer-Binding Protein-alpha physiology, Gene Expression Regulation immunology, Myeloid Cells immunology, Myeloid Cells metabolism, Promoter Regions, Genetic immunology, Proto-Oncogene Proteins physiology, Receptors, Fc genetics, Receptors, Fc metabolism, Transcription Factors physiology
- Abstract
Fc alpha R (CD89), the FcR for IgA, is expressed exclusively in myeloid cells, including monocytes/macrophages, neutrophils, and eosinophils, and is thought to mediate IgA-triggered cellular functions in immunity. Here we demonstrate that the Fc alpha R 5'-flanking region from -102 to -64 relative to the ATG translation initiation codon is essential for promoter activity and contains two functional binding motifs for C/EBP and Ets family members at -74 and -92, respectively. EMSAs and cotransfection experiments show that C/EBP alpha acts as a major activator of the Fc alpha R promoter at least in immature myeloid cells. In addition, we found two additional functional targets of C/EBP alpha at -139 and -127. On the other hand, the Fc alpha R Ets binding motif could bind Elf-1 and mediate the trans-activation by cotransfected Elf-1, but a major component of the complex forming on this site appears to be an unidentified Ets-like nuclear protein that is preferentially detected in cells of hemopoietic origin. Furthermore, separation of the C/EBP and Ets binding sites reduces Fc alpha R promoter activity, suggesting some functional interaction between these factors. As the in vivo role of Fc alpha R is still incompletely defined, these findings reveal the features controlling the Fc alpha R promoter in myeloid lineage and provide a foundation for clarifying regulatory mechanisms of Fc alpha R gene expression associated with its potential roles.
- Published
- 2003
- Full Text
- View/download PDF
17. Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses.
- Author
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Xiu Y, Nakamura K, Abe M, Li N, Wen XS, Jiang Y, Zhang D, Tsurui H, Matsuoka S, Hamano Y, Fujii H, Ono M, Takai T, Shimokawa T, Ra C, Shirai T, and Hirose S
- Subjects
- Alleles, Animals, Antibody Formation genetics, Antigens, CD biosynthesis, B-Lymphocytes immunology, B-Lymphocytes metabolism, Binding Sites genetics, Binding Sites immunology, Cell Line, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Gene Expression Regulation genetics, Germinal Center cytology, Germinal Center immunology, Germinal Center metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred NZB, Mice, Knockout, Receptors, IgG biosynthesis, Sequence Homology, Nucleic Acid, Spleen cytology, Spleen immunology, Spleen metabolism, Transcription Factors genetics, Transcription Factors metabolism, Transcription, Genetic genetics, Tumor Cells, Cultured, Antigens, CD genetics, Antigens, CD metabolism, Gene Expression Regulation immunology, Polymorphism, Genetic immunology, Promoter Regions, Genetic immunology, Receptors, IgG genetics, Receptors, IgG metabolism, Transcription, Genetic immunology
- Abstract
FcgammaRIIB1 molecules serve as negative feedback regulator for B cell Ag receptor-elicited activation of B cells; thus, any impaired FcgammaRIIB1 function may possibly be related to aberrant B cell activation. We earlier found deletion polymorphism in the Fcgr2b promoter region among mouse strains in which systemic autoimmune disease-prone NZB, BXSB, MRL, and autoimmune diabetes-prone nonobese diabetic, but not NZW, BALB/c, and C57BL/6 mice have two identical deletion sites, consisting of 13 and 3 nucleotides. In this study, we established congenic C57BL/6 mice for NZB-type Fcgr2b allele and found that NZB-type allele down-regulates FcgammaRIIB1 expression levels in germinal center B cells and up-regulates IgG Ab responses. We did luciferase reporter assays to determine whether NZB-type deletion polymorphism affects transcriptional regulation of Fcgr2b gene. Although NZW- and BALB/c-derived segments from position -302 to +585 of Fcgr2b upstream region produced significant levels of luciferase activities, only a limited activity was detected in the NZB-derived sequence. EMSA and Southwestern analysis revealed that defect in transcription activity in the NZB-derived segment is likely due to absence of transactivation by AP-4, which binds to the polymorphic 13 nucleotide deletion site. Our data imply that because of the deficient AP-4 binding, the NZB-type Fcgr2b allele polymorphism results in up-regulation of IgG Ab responses through down-regulation of FcgammaRIIB1 expression levels in germinal center B cells, and that such polymorphism may possibly form the basis of autoimmune susceptibility in combination with other background contributing genes.
- Published
- 2002
- Full Text
- View/download PDF
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