論文 - 詳細
| RRC ID | 78152 |
|---|---|
| 著者 | Segawa R, Kyoda T, Yagisawa M, Muramatsu T, Hiratsuka M, Hirasawa N. |
| タイトル | Hypoxia-inducible factor prolyl hydroxylase inhibitors suppressed thymic stromal lymphopoietin production and allergic responses in a mouse air-pouch-type ovalbumin sensitization model. |
| ジャーナル | Int Immunopharmacol |
| Abstract |
Atopic dermatitis (AD) is an allergic skin disease, triggered by excessive type 2 immune reactions. Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune response through dendritic cell activation. Therefore, TSLP inhibitors may serve as novel antiallergic drugs. Hypoxia-inducible factor (HIF) activation in the epithelia contributes to several homeostatic phenomena, such as re-epithelialization. However, the effects of HIF activation on TSLP production and immune activation in the skin remain unclear. In this study, we found that selective HIF prolyl hydroxylase inhibitors (PHD inhibitors), which induce HIF activation, suppressed TSLP production in a mouse ovalbumin (OVA) sensitization model. PHD inhibitors also suppressed the production of tumor necrosis factor-alpha (TNF-α), which is a major inducer of TSLP production, in this mouse model and in a macrophage cell line. Consistent with these findings, PHD inhibitors suppressed OVA-specific IgE levels in the serum and OVA-induced allergic responses. Furthermore, we found a direct suppressive effect on TSLP expression in a human keratinocyte cell line mediated by HIF activation. Taken together, our findings suggest that PHD inhibitors exert antiallergic effects by suppressing TSLP production. Controlling the HIF activation system has therapeutic potential in AD. |
| 巻・号 | 118 |
| ページ | 110127 |
| 公開日 | 2023-5-1 |
| DOI | 10.1016/j.intimp.2023.110127 |
| PII | S1567-5769(23)00448-4 |
| PMID | 37030118 |
| MeSH | Animals Cytokines / metabolism Dermatitis, Atopic* / drug therapy Humans Hypoxia Mice Ovalbumin / therapeutic use Prolyl Hydroxylases / metabolism Prolyl-Hydroxylase Inhibitors* / pharmacology Prolyl-Hydroxylase Inhibitors* / therapeutic use Thymic Stromal Lymphopoietin / metabolism |
| IF | 3.943 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |