Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells.
The functional role of C-terminal binding protein (CtBP)1, a transcriptional corepressor, in Th1 and Th2 cytokine expression in human T cells was investigated. Upon introduction of CtBP1 by lentiviral transduction system, IL-4 synthesis was suppressed but IFN-gamma was weakly up-regulated in human CD4(+) T cells. In contrast, a reduction of endogenously expressed CtBP1 in Jurkat T cells using RNAi technology selectively augmented IL-4 expression. The down-regulation of IL-4 by CtBP1 was achieved at the level of gene transcription. Deletion mutation analysis revealed that N-terminal approximately 200 amino acid and C-terminal approximately 50 amino acid residues are participated in CtBP1-mediated suppression of IL-4 expression. CtBP1 expressed in human CD4(+) T cells crucially contribute to Th1/Th2 differentiation via selective down-regulation of IL-4 synthesis.
Kitamura
Noriko
N
Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.
Motoi
Yuji
Y
Mori
Akio
A
Tatsumi
Hideki
H
Nemoto
Soichi
S
Miyoshi
Hiroyuki
H
Kitamura
Fujiko
F
Miyatake
Shoichiro
S
Hiroi
Takachika
T
Kaminuma
Osamu
O
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells; D017384:Sequence Deletion; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D015847:Interleukin-4; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein