| RRC ID |
18166
|
| 著者 |
Kanada S, Nishiyama C, Nakano N, Suzuki R, Maeda K, Hara M, Kitamura N, Ogawa H, Okumura K.
|
| タイトル |
Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells.
|
| ジャーナル |
Blood
|
| Abstract |
In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases.
|
| 巻・号 |
117(7)
|
| ページ |
2211-22
|
| 公開日 |
2011-2-17
|
| DOI |
10.1182/blood-2010-06-291898
|
| PII |
S0006-4971(20)55101-X
|
| PMID |
21119111
|
| MeSH |
Administration, Topical
Animals
B7-1 Antigen / genetics
B7-1 Antigen / metabolism*
B7-2 Antigen / genetics
B7-2 Antigen / metabolism*
Base Sequence
Binding Sites / genetics
DNA, Complementary / genetics
Dendritic Cells / immunology*
Dendritic Cells / metabolism*
Dermatitis, Contact / genetics
Dermatitis, Contact / immunology
Dermatitis, Contact / prevention & control
Down-Regulation
Female
In Vitro Techniques
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Promoter Regions, Genetic
Proto-Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Trans-Activators / antagonists & inhibitors
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcription Initiation Site
Transcriptional Activation
|
| IF |
17.794
|
| 引用数 |
35
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
CV-1(RCB0160) |
