Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients.
BACKGROUND
Helper T cells and T cell cytokines play central roles in allergic disorders including bronchial asthma. We reported enhanced IL-5 production by peripheral blood T cells of asthmatic patients. A transcription factor, GATA-3, has been implicated in IL-5 gene expression. This study was undertaken to clarify the role of GATA-3 in the upregulation of IL-5 synthesis in asthmatic patients.


METHODS
Peripheral CD4+ T cells were transfected with an IL-5 promoter reporter construct as well as its mutants in the presence or absence of a GATA-3 expression vector. Messenger RNA expression level of GATA-3 in CD4+ T cells of asthmatic subjects was compared to that of healthy donors.


RESULTS
IL-5 promoter activity in CD4+ T cells was enhanced by overexpression of GATA-3, whereas it was diminished by the introduction of mutations in the putative GATA-3 binding sites. The GATA-3 expression level in CD4+ T cells of asthmatic patients was equivalent to that of healthy controls.


CONCLUSIONS
The expression level of GATA-3 may not be an essential factor to cause IL-5 hyperproduction in bronchial asthma, though GATA-3 is crucially involved in IL-5 gene transcription in human peripheral CD4+ T cells.
Kaminuma
Osamu
O
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Mori
Akio
A
Kitamura
Noriko
N
Hashimoto
Tomomi
T
Kitamura
Fujiko
F
Inokuma
Shigeko
S
Miyatake
Shoichiro
S
D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D050990:GATA3 Transcription Factor; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015848:Interleukin-5; D012333:RNA, Messenger; D015534:Trans-Activators; D049452:Green Fluorescent Proteins