The Human IgE Germline Promoter is Regulated By Interleukin-4, Interleukin-13, Interferon-alpha and Interferon-gamma Via an Interferon-gamma-Activated Site and Its Flanking Regions

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Abstract
Class switching to IgE is preceded by the appearance of ɛ germline transcripts, which are induced by Interleukin‐4 (IL‐4) and by IL‐13. A 51‐bp fragment of the human ɛ germline promoter conferred in reporter gene assays with the erythroleukemic cell line TF‐1 upregulation of transcription by IL‐4 or IL‐13, and repression by interferon‐α (IFN‐α) and IFN‐γ. A central IFN‐γ activated sequence within the 51‐bp fragment was sufficient for transcriptional regulation by the cytokines in the absence of its normal flanking regions. In contrast, deletion of either upstream or downstream sequences abolished repression by IFN‐α or INF‐γ, but not upregulation by IL‐4 or IL‐13. IL‐4 stimulated reporter gene transcription required more than ten times higher concentrations than cell proliferation or tyrosine phosphorylation of the IL‐4 receptor.