Downregulation of IL-13 gene transcription by T-bet in human T cells.
BACKGROUND
Downregulation of a Th2 cytokine, IL-4, by a Th1-specific transcription factor, T-bet, has been demonstrated. However, the regulatory role of T-bet in another Th2 cytokine, IL-13, is not fully delineated.


METHODS
IL-13 mRNA expression in Jurkat cells was examined by quantitative RT-PCR, while the transcriptional activity of 5'-flanking region in the IL-13 gene encompassing -1077 to +49 was investigated by fluorescence-based promoter reporter assay. The effect of T-bet was investigated by transfection of the cells with the T-bet expression vector.


RESULTS
Stimulation with phorbol ester plus Ca2+ ionophore clearly induced IL-13 gene transcription in Jurkat cells. Ectopically expressed T-bet significantly suppressed the inducible mRNA expression and promoter activity of IL-13.


CONCLUSIONS
IL-13 expression was downregulated by T-bet at the level of gene transcription, independently of the modulation of Th1/Th2 balance. T-bet is the potential key factor in the development of Th1/Th2-related diseases.
Suzuki
Kazuya
K
Department of Allergy and Immunology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Kaminuma
Osamu
O
Hiroi
Takachika
T
Kitamura
Fujiko
F
Miyatake
Shoichiro
S
Takaiwa
Fumio
F
Tatsumi
Hideki
H
Nemoto
Soichi
S
Kitamura
Noriko
N
Mori
Akio
A
D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic; D000098815:T-bet Transcription Factor
D018793:Interleukin-13; D007476:Ionophores; D010703:Phorbol Esters; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D002118:Calcium