Involvement of PU.1 in Mast Cell/Basophil-Specific Function of the Human <i>IL1RL1/ST2</i> Promoter

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Author(s)

    • Baba Yosuke
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine|Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine
    • Ogawa Hideoki
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine
    • Okumura Ko
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine
    • Maeda Keiko
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine
    • Yashiro Takuya
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine
    • Inage Eisuke
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine|Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine
    • Hara Mutsuko
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine
    • Suzuki Ryuyo
    • Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine
    • Ohtsuka Yoshikazu
    • Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine
    • Shimizu Toshiaki
    • Atopy (Allergy) Research Center, Juntendo University School of Medicine|Department of Pediatrics and Adolescence Medicine, Juntendo University School of Medicine

Abstract

<b>Background:</b> The human <i>IL1RL1/ST2</i> gene encodes IL33 receptor. Recently, IL33 has been recognized as a key molecule for the development of Th2 response. Although mast cells and basophils are major targets of IL33 and play important roles in IL33-mediated Th2-type immune responses, the expression mechanism of ST2 in mast cells and basophils is largely unknown. In the present study, we analyzed regulation mechanism of the human <i>ST2</i> promoter in the human mast cell line LAD2 and basophilic cell line KU812.<br> <b>Methods:</b> Promoter activity was determined by reporter assay with plasmids carrying the wild-type <i>ST2</i> promoter obtained from human genomic DNA and its mutant. The transcription factor binding to the identified <i>cis</i>-element was identified by an electrophoretic mobility shift assay (EMSA). The effect of candidate transcription factor on ST2 expression was confirmed by analyzing ST2 mRNA level in siRNA-introduced cells.<br> <b>Results:</b> Reporter assay demonstrated that a <i>cis</i>-element of typical Ets-family binding sequence was critical for promoter activity in LAD2 and KU812. An Ets-family transcription factor PU.1 bound to this element in an EMSA. When PU.1 expression was suppressed by siRNA, ST2 mRNA level was significantly reduced in KU812.<br> <b>Conclusions:</b> These observations indicated that PU.1 positively regulates the <i>ST2</i> promoter as a transcription factor that directly transactivates the <i>ST2</i> promoter via Ets-family-related <i>cis</i>-element in mast cells and basophils.<br>

Journal

  • Allergology International

    Allergology International 61(3), 461-467, 2012

    Japanese Society of Allergology

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