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

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 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 α 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.