論文 - 詳細
| RRC ID | 39848 |
|---|---|
| 著者 | Oyama N, Iwatsuki K, Satoh M, Akiba H, Kaneko F. |
| タイトル | Dermal fibroblasts are one of the therapeutic targets for topical application of 1alpha,25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-beta induction. |
| ジャーナル | Br J Dermatol |
| Abstract |
BACKGROUND:Transforming growth factor (TGF) -beta has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-beta are biologically latent complexes, activation is essential for TGF-beta-mediated cellular responses in vitro and in vivo. Objectives Here we report the response of the TGF-beta regulation system to 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques. RESULTS:1,25(OH)2D3 caused a dose-dependent induction of latent and active TGF-beta1 proteins in both cell cultures. The increases were significant over 72 h, but not within 48 h after stimulation. The time course of TGF-beta1 mRNA expression showed a biphasic response consisting of early ( approximately 1 h) and late phases ( approximately 96 h) of induction. Concomitant increases of TGF-beta2 and -beta3, other mammalian isoforms, were observed in the 1,25(OH)2D3-treated cells, but the kinetics were all different. Co-incubation with metabolic inhibitors, actinomycin D and cycloheximide, revealed that the early induction of TGF-beta1 mRNA by 1,25(OH)2D3 is dependent on de novo RNA synthesis, but not on RNA stabilization or protein synthesis. It seems likely to be a transient and negligible response given the absence of TGF-beta1 protein production. The late induction of TGF-beta1 mRNA was partially blocked by adding isoform-specific antibodies to TGF-beta1, -beta2 and -beta3, indicating TGF-beta autoregulation. Despite these marked responses, there were no significant differences in the TGF-beta expression between normal and psoriatic fibroblasts. CONCLUSIONS:These results suggest that antiproliferative and anti-inflammatory effects of 1,25(OH)2D3 on psoriatic lesional skin may be mediated, at least in part, by a complex TGF-beta regulation in local dermal fibroblasts. |
| 巻・号 | 143(6) |
| ページ | 1140-8 |
| 公開日 | 2000-12-1 |
| DOI | 10.1046/j.1365-2133.2000.03880.x |
| PII | bjd3880 |
| PMID | 11122013 |
| MeSH | Administration, Topical Adult Blotting, Northern Calcitriol / therapeutic use* Cells, Cultured Fibroblasts / drug effects* Fibroblasts / metabolism Humans Psoriasis / drug therapy* Psoriasis / metabolism Psoriasis / pathology RNA, Messenger / metabolism Transforming Growth Factor beta / metabolism* Transforming Growth Factor beta1 Transforming Growth Factor beta2 Transforming Growth Factor beta3 |
| IF | 7.0 |
| 引用数 | 19 |
| WOS 分野 | DERMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Mv.1.Lu(NBL-7)(RCB0996) |