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Identification of a Stat-6-Responsive Element in the Promoter of the Human Interleukin-4 Gene

  1. Author:
    Curiel, R. E.
    Lahesmaa, R.
    Subleski, J.
    Cippitelli, M.
    Kirken, R. A.
    Young, H. A.
    Ghosh, P.

  2. Author Address

    Ghosh P UNIV MIAMI SCH MED DEPT MICROBIOL & IMMUNOL MIAMI, FL 33136 USA NCI FREDERICK CANC RES & DEV CTR EXPT IMMUNOL LAB DIV BASIC SCI FREDERICK, MD USA NCI FREDERICK CANC RES & DEV CTR INTRAMURAL RES SUPPORT PROGRAM SAIC FREDERICK FREDERICK, MD USA ROCHE BIOSCI DEPT LEUKOCYTE BIOL PALO ALTO, CA USA
    1. Year: 1997
  2. Journal: European Journal of Immunology
    1. 27
    2. 8
    3. Pages: 1982-1987
  4. Type of Article: Article
  1. Abstract:

    Interleukin (IL)-4 is an immunomodulatory cytokine produced by a number of cell types including T cells, basophils, and mast cells. This pleiotropic cytokine has a number of immunoregulatory functions; however, the molecular mechanisms controlling the transcription of this gene are nor yet completely understood. Several studies have implicated a possible autoregulatory mechanism for its own expression. Here, we have identified a Stat-6-responsive element (Stat-6RE) in the promoter of the human IL-4 gene. Utilizing electrophoretic mobility shift analysis, we have demonstrated the presence of two specific IL-4-responsive DNA-protein complexes in nuclear extracts of both human Th1 and Th2 clones. Phytohemagglutinin-blasted peripheral blood T cells also generated an inducible complex in response to stimulation with IL-4 and the IL-4-like cytokine IL-13. Transient transfection of the murine pre-B cell line BA/F3 stably transfected with the full-length human IL-4 receptor alpha chain demonstrated the ability of multicopy Stat-6RE to initiate transcription from a heterologous promoter upon IL-4 or IL-13 stimulation. These results indicate a possible autocrine mechanism for the regulation of IL-4 gene transcription through the Stat-6RF, as well as a possible mechanism for IL-13 regulation of the human IL-4 promoter. [References: 37]

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