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.
Curiel
R E
RE
Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, USA.
Lahesmaa
R
R
Subleski
J
J
Cippitelli
M
M
Kirken
R A
RA
Young
H A
HA
Ghosh
P
P
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000235:genetics* / Q000494:pharmacology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection
D018793:Interleukin-13; D009838:Oligodeoxyribonucleotides; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D015500:Chloramphenicol O-Acetyltransferase