The interaction between GATA proteins and activator protein-1 promotes the transcription of IL-13 in mast cells.
IL-13 is considered to be a key modulator in the pathogenesis of Th2-induced allergic inflammation, although little is known about the regulation of IL-13 transcription in mast cells. In T cells, involvement of GATA-3 in cell type-specific expression of the IL-13 gene has been reported. However, the mechanisms that induce rapid transactivation of the IL-13 gene in response to various types of stimulation have hitherto remained unknown. In this report, we describe our investigation of the promoter region necessary for IL-13 transcription; we have found that both AP-1 and GATA proteins are indispensable for IL-13 transcription in mouse mast cells. In our investigation, we focused on the functional interaction between GATA and AP-1 in the IL-13 promoter context. Transfection experiments have revealed that GATA-1 and GATA-2 proteins are able to associate with AP-1 proteins. We have also shown that overexpression of GATA-1 induced excess AP-1 binding to the IL-13 promoter as well as a significant increase in IL-13 production in mast cells. The results of the present study have shown that direct interaction between AP-1 and GATA proteins plays an important role in IL-13 transcription in mast cells.
Masuda
Akio
A
Division of Host Defense, Center for Neural Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan. amasuda@med.nagoya-u.ac.jp
Yoshikai
Yasunobu
Y
Kume
Hiroaki
H
Matsuguchi
Tetsuya
T
D020121:5' Untranslated Regions / Q000737:chemistry / Q000502:physiology; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic / Q000276:immunology*; D014162:Transfection
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D010446:Peptide Fragments; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors