論文 - 詳細
| RRC ID | 27172 |
|---|---|
| 著者 | Nakajima Y, Nakamura Y, Shigeeda W, Tomoyasu M, Deguchi H, Tanita T, Yamauchi K. |
| タイトル | The role of tumor necrosis factor-α and interferon-γ in regulating angiomotin-like protein 1 expression in lung microvascular endothelial cells. |
| ジャーナル | Allergol Int |
| Abstract |
BACKGROUND:Angiogenesis in the alveolar septa is thought be a critical factor in pulmonary emphysema. Angiomotin-like protein 1 (AmotL1) is involved in angiogenesis via regulating endothelial cell function. However, the role of AmotL1 in the pathogenesis of pulmonary emphysema has not been elucidated. The objective of this study is to evaluate the expression of AmotL1 in lung tissues from a murine model with emphysema, as well as from patients with chronic obstructive pulmonary disease (COPD). Furthermore, we analyzed the regulation of AmotL1 expression by TNF-α and IFN-γ in endothelial cells in vitro. METHODS:Nrf2 knockout mice were exposed to cigarette smoke (CS) for 4 weeks, and the down-regulated genes affecting vascularity in the whole lung were identified by microarray analysis. This analysis revealed that the mRNA expression of AmotL1 decreased in response to CS when compared with air exposure. To confirm the protein levels that were indicated in the microarray data, we determined the expression of AmotL1 in lung tissues obtained from patients with COPD and also determined the expression of AmotL1, NFκB and IκBα in cultured normal human lung microvascular endothelial cells (HLMVECs) that were stimulated by TNF-α and IFN-γ. RESULTS:We found that the number of AmotL1-positive vessels decreased in the emphysema lungs compared with the normal and bronchial asthmatic lungs. IFN-γ pretreatment diminished the TNF-α-induced AmotL1 in the cultured HLMVECs by blocking the degradation of IκBα. CONCLUSIONS:These results suggested that IFN-γ exhibits anti-angiogenesis effects by regulating the expression of TNF-α-induced AmotL1 via NFκB in emphysema lungs. |
| 巻・号 | 62(3) |
| ページ | 309-22 |
| 公開日 | 2013-9-1 |
| DOI | 10.2332/allergolint.12-OA-0528 |
| PII | S1323-8930(15)30144-1 |
| PMID | 23793505 |
| MeSH | Angiomotins Angiopoietin-Like Protein 1 Animals Cell Line Disease Models, Animal Down-Regulation* Endothelial Cells / immunology Endothelial Cells / metabolism* Endothelial Cells / pathology Humans I-kappa B Kinase / genetics I-kappa B Kinase / immunology I-kappa B Kinase / metabolism Interferon-gamma / genetics Interferon-gamma / immunology Interferon-gamma / metabolism* Membrane Proteins / biosynthesis* Membrane Proteins / genetics Membrane Proteins / immunology Mice Mice, Knockout NF-kappa B / genetics NF-kappa B / immunology NF-kappa B / metabolism Neovascularization, Pathologic / chemically induced Neovascularization, Pathologic / genetics Neovascularization, Pathologic / immunology Neovascularization, Pathologic / metabolism* Neovascularization, Pathologic / pathology Pulmonary Alveoli / blood supply Pulmonary Alveoli / immunology Pulmonary Alveoli / metabolism* Pulmonary Alveoli / pathology Pulmonary Emphysema / chemically induced Pulmonary Emphysema / genetics Pulmonary Emphysema / immunology Pulmonary Emphysema / metabolism* Pulmonary Emphysema / pathology Tobacco Smoke Pollution / adverse effects Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism* |
| IF | 4.806 |
| 引用数 | 4 |
| WOS 分野 | ALLERGY IMMUNOLOGY |
| リソース情報 | |
| 実験動物マウス | RBRC01390 |