Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells.
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.
Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Shunsuke
S
Kanada
Chiharu
C
Nishiyama
Nobuhiro
N
Nakano
Ryuyo
R
Suzuki
Keiko
K
Maeda
Mutsuko
M
Hara
Nao
N
Kitamura
Hideoki
H
Ogawa
Ko
K
Okumura
D000287:Administration, Topical; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D015536:Down-Regulation; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D000099232:Proto-Oncogene Protein Spi-1
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C497965:Cd86 protein, mouse