論文 - 詳細
| RRC ID | 3818 |
|---|---|
| 著者 | Adachi T, Hanaka S, Masuda T, Yoshihara H, Nagase H, Ohta K. |
| タイトル | Transduction of phosphatase and tensin homolog deleted on chromosome 10 into eosinophils attenuates survival, chemotaxis, and airway inflammation. |
| ジャーナル | J Immunol |
| Abstract |
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN antagonizes the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. In the present study, we used a TAT fusion protein transduction system to elucidate the role of PTEN in eosinophils and airway inflammation. A small region of the HIV TAT protein (YGRKKRRQRRR), a protein transduction domain known to enter mammalian cells efficiently, was fused to the N terminus of PTEN. Flow cytometric analysis of annexin V- and propidium iodide-stained cells was used to assess eosinophil survival. A chemotaxis assay was performed using a Boyden chamber. Cell analysis in bronchoalveolar lavage fluid and histological examinations were performed using OVA-challenged A/J mice. We found that TAT-PTEN was successfully internalized into eosinophils and functioned as a phosphatase in situ. TAT-PTEN, but not a TAT-GFP control protein, blocked the ability of IL-5 to prevent the apoptosis of eosinophils from allergic subjects. The eotaxin-induced eosinophil chemotaxis was inhibited by TAT-PTEN in a dose-dependent manner. Intranasal pretreatment with TAT-PTEN, but not TAT-GFP, significantly inhibited the OVA-induced eosinophil infiltration in bronchoalveolar lavage fluid. Histological examination of the lung, including H&E and Alcian blue/periodic acid-Schiff staining, revealed that TAT-PTEN, but not TAT-GFP, abrogated eosinophilic inflammation and mucus production. Our results suggest that PTEN negatively regulates eosinophil survival, chemotaxis, and allergic inflammation. The pharmacological targeting of PTEN may constitute a new strategy for the treatment of eosinophilic disorders. |
| 巻・号 | 179(12) |
| ページ | 8105-11 |
| 公開日 | 2007-12-15 |
| DOI | 10.4049/jimmunol.179.12.8105 |
| PII | 179/12/8105 |
| PMID | 18056352 |
| MeSH | Amino Acid Sequence Animals Cell Survival Chemotaxis* Eosinophils / enzymology Eosinophils / immunology* Humans Mice Mice, Inbred Strains Molecular Sequence Data PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism* Pneumonia / immunology* Pneumonia / pathology Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transduction, Genetic tat Gene Products, Human Immunodeficiency Virus / genetics tat Gene Products, Human Immunodeficiency Virus / metabolism |
| IF | 4.886 |
| 引用数 | 11 |
| WOS 分野 | IMMUNOLOGY |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 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 | |
| 遺伝子材料 | pAxCAhPTEN1(RDB02013) |