Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene

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 not 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-6RE as well as a possible mechanism for IL-13 regulation of the human IL-4 promoter.