A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer

Greg Henkel, Deborah L. Weiss, Randy McCoy, Thomas Deloughery, David Tara, Melissa A. Brown

    Research output: Contribution to journalArticle

    70 Citations (Scopus)

    Abstract

    IL-4 is a potent immunoregulatory cytokine that exhibits extremely diverse effects on a number of target cells. Although IL-4 was originally described as a T cell-derived product, it is evident that cells of the basophil/mast cell lineage are also an important source of this cytokine. Based on their different tissue distribution, mast cell and T cell-derived IL-4 may have distinct effects on local immune responses. The physiologic production of IL-4 appears to be tightly regulated because most T and mast cells require activation to express significant levels of IL-4. In contrast, a majority of murine transformed mast cell lines constitutively express relatively high levels of IL-4. In this study, transformed mast cell lines were used as models to define cis acting sequences that regulate mast cell IL-4 transcription. Chloramphenicol acetyltransferase reporter gene constructs containing 6.3 kb of 5′ IL-4 flanking sequence direct relatively low chloramphenicol acetyltransferase expression in these cells. These results indicated that additional sequences may be important in stimulating transcriptional activity of the IL-4 gene. Using DNAse I hypersensitive site analysis to define other potential IL-4 transcriptional regulatory regions, two sites were identified in the murine IL-4 gene that appear to be unique to IL-4 expressing transformed mast cells. One site defines an intronic sequence that exhibits prototypic enhancer activity in several independently derived transformed mast cell lines. This enhancer is also active in stimulated, non-transformed mast cells but not stimulated EL-4 T cells. Taken together, these data indicate that the IL-4 intronic sequence contains a mast cell specific enhancer that plays an essential role in the unregulated expression of IL-4 in transformed mast cells and may also be important in the inducible expression of IL-4 in normal mast cells.

    Original languageEnglish (US)
    Pages (from-to)3239-3246
    Number of pages8
    JournalJournal of Immunology
    Volume149
    Issue number10
    StatePublished - 1992

    Fingerprint

    Deoxyribonuclease I
    Mast Cells
    Interleukin-4
    Introns
    Genes
    Transformed Cell Line
    T-Lymphocytes
    Chloramphenicol O-Acetyltransferase
    Cytokines
    Basophils
    Nucleic Acid Regulatory Sequences
    Cell Lineage
    Tissue Distribution
    Reporter Genes

    ASJC Scopus subject areas

    • Immunology

    Cite this

    A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer. / Henkel, Greg; Weiss, Deborah L.; McCoy, Randy; Deloughery, Thomas; Tara, David; Brown, Melissa A.

    In: Journal of Immunology, Vol. 149, No. 10, 1992, p. 3239-3246.

    Research output: Contribution to journalArticle

    Henkel, Greg ; Weiss, Deborah L. ; McCoy, Randy ; Deloughery, Thomas ; Tara, David ; Brown, Melissa A. / A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer. In: Journal of Immunology. 1992 ; Vol. 149, No. 10. pp. 3239-3246.
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    AU - Henkel, Greg

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