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Suppressive effect of Elf-1 on FcεRI α-chain expression in primary mast cells

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Abstract

The high-affinity receptor for immunoglobulin E (IgE), FcεRI, is specifically expressed in mast cells and basophils and plays a key role in IgE-mediated allergic reactions. The transcription factor Elf-1 has been previously identified to bind to the promoter of the human FcεRI α-chain, which is essential for the function and expression of FcεRI. In the present study, Elf-1 siRNA was conducted to evaluate the effects of Elf-1 on FcεRI α-chain expression in the primary mouse mast cells, bone marrow-derived mast cells (BMMC). Introduction of Elf-1 siRNA effectively reduced expression levels of Elf-1 mRNA and protein in BMMC. Transient reporter assay showed that the knockdown of Elf-1 by siRNA resulted in increased FcεRI α-chain promoter activity, while overexpression of Elf-1 suppressed α-chain promoter activity in BMMC. Elf-1 siRNA-treated BMMC exhibited marked upregulation of FcεRI α-chain transcription, whereas β-chain mRNA was not affected by Elf-1 siRNA. Chromatin immunoprecipitation assay showed that the amount of transcription factor PU.1, recognizing the cis-element close to the Elf-1-site on the FcεRI α-chain promoter, was significantly increased by introduction of Elf-1 siRNA. These results indicate that Elf-1 negatively regulates FcεRI α-chain expression by suppressing PU.1-mediated transcription of the α-chain in BMMC.

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Abbreviations

BMMC:

bone marrow-derived mast cells

ChIP:

chromatin immunoprecipitation

Ct:

cycle threschold

EMSA:

electrophoretic mobility shift assay

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Acknowledgments

We would like to thank members of the Atopy (Allergy) Research Center and the Department of Immunology for helpful discussions. We are grateful for Drs. Y. Niwa, T. Fukai, and D. Potaczek for their technical assistance and Ms. M. Matsumoto for secretarial assistance. This work was supported in part by a grant-in-aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to C. N.).

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Authors and Affiliations

  1. Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Qing-hui Wang, Chiharu Nishiyama, Nobuhiro Nakano, Naomi Shimokawa, Mutsuko Hara, Shunsuke Kanada, Hideoki Ogawa & Ko Okumura

  2. Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Shunsuke Kanada & Ko Okumura

  3. Department of Immunology, College of Basic Medical Sciences, China Medical University, No. 92 Beier Road, Heping District, Shenyang, China

    Qing-hui Wang

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  1. Qing-hui Wang
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  2. Chiharu Nishiyama
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  3. Nobuhiro Nakano
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  4. Naomi Shimokawa
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  5. Mutsuko Hara
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  8. Ko Okumura
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Correspondence to Chiharu Nishiyama.

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Wang, Qh., Nishiyama, C., Nakano, N. et al. Suppressive effect of Elf-1 on FcεRI α-chain expression in primary mast cells. Immunogenetics 60, 557–563 (2008). https://doi.org/10.1007/s00251-008-0318-y

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  • DOI: https://doi.org/10.1007/s00251-008-0318-y

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