Cell Type-Dependent Divergence of Transactivation by Glucocorticoid Receptor Ligand.
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- Tanigawa Kiyoshi
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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- Tanaka Katsunao
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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- Nagase Hideki
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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- Miyake Hidekazu
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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- Kiniwa Mamoru
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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- Ikizawa Koichi
- Pharmacobioregulation Research Laboratory, Taiho Pharmaceutical Co., Ltd.
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抄録
The glucocorticoid receptor regulates gene expression mainly by two mechanisms; transactivation and trans-repression. A ligand with strong transrepression and weak transactivation activity is predicted to be a beneficial agent with potent anti-inflammatory activity and minor adverse effects. Recently, the profile of a synthetic steroid, RU24858, has been reported to fulfill this condition in vitro, but others have reported no dissociation between the anti-inflammatory activity and side effects in vivo. To gain further information on the profile of this compound, we evaluated its transactivation ability using a reporter gene analysis both in vitro and in vivo. In the in vitro analysis, RU24858 demonstrated only a weak transactivation activity in HeLa cells, when compared with prednisolone. In CV-1 cells, however, these two glucocorticoids exhibited equivalent transactivation activities. This behavior is independent of whether the reporter gene is regulated by mouse mammary tumor virus promoter or multiple copies of glucocorticoid response element. When the reporter plasmid was inoculated into mouse abdominal skin using a gene gun, followed by orally administration of glucocorticoids, RU24858 induced significantly higher reporter enzyme activity than prednisolone. These results suggest that the profile of RU24858 is divergent and its transactivation ability is comparable to prednisolone depending on the cell-type both in vitro and in vivo.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 25 (12), 1619-1622, 2002
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204624604416
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- NII論文ID
- 130000111737
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3sXktFKi
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 6371147
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- PubMed
- 12499651
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可