The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells
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 elucidat...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2013-01-01
|
Series: | Allergology International |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1323893015301441 |
id |
doaj-953aa0a4960f4b008ac4e9df3908c0de |
---|---|
record_format |
Article |
spelling |
doaj-953aa0a4960f4b008ac4e9df3908c0de2020-11-24T22:55:06ZengElsevierAllergology International1323-89302013-01-0162330932210.2332/allergolint.12-OA-0528The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial CellsYoshio Nakajima0Yutaka Nakamura1Wataru Shigeeda2Makoto Tomoyasu3Hiroyuki Deguchi4Tatsuo Tanita5Kohei Yamauchi6Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate, Japan.Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate, Japan.Department of Thoracic Surgery, Iwate Medical University School of Medicine, Iwate, Japan.Department of Thoracic Surgery, Iwate Medical University School of Medicine, Iwate, Japan.Department of Thoracic Surgery, Iwate Medical University School of Medicine, Iwate, Japan.Department of Thoracic Surgery, Iwate Medical University School of Medicine, Iwate, Japan.Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate, Japan.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.http://www.sciencedirect.com/science/article/pii/S1323893015301441angiogenesisangiomotinangiomotin-like protein 1COPDemphysema |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yoshio Nakajima Yutaka Nakamura Wataru Shigeeda Makoto Tomoyasu Hiroyuki Deguchi Tatsuo Tanita Kohei Yamauchi |
spellingShingle |
Yoshio Nakajima Yutaka Nakamura Wataru Shigeeda Makoto Tomoyasu Hiroyuki Deguchi Tatsuo Tanita Kohei Yamauchi The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells Allergology International angiogenesis angiomotin angiomotin-like protein 1 COPD emphysema |
author_facet |
Yoshio Nakajima Yutaka Nakamura Wataru Shigeeda Makoto Tomoyasu Hiroyuki Deguchi Tatsuo Tanita Kohei Yamauchi |
author_sort |
Yoshio Nakajima |
title |
The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells |
title_short |
The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells |
title_full |
The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells |
title_fullStr |
The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells |
title_full_unstemmed |
The Role of Tumor Necrosis Factor-α and Interferon-γ in Regulating Angiomotin-Like Protein 1 Expression in Lung Microvascular Endothelial Cells |
title_sort |
role of tumor necrosis factor-α and interferon-γ in regulating angiomotin-like protein 1 expression in lung microvascular endothelial cells |
publisher |
Elsevier |
series |
Allergology International |
issn |
1323-8930 |
publishDate |
2013-01-01 |
description |
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. |
topic |
angiogenesis angiomotin angiomotin-like protein 1 COPD emphysema |
url |
http://www.sciencedirect.com/science/article/pii/S1323893015301441 |
work_keys_str_mv |
AT yoshionakajima theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT yutakanakamura theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT watarushigeeda theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT makototomoyasu theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT hiroyukideguchi theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT tatsuotanita theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT koheiyamauchi theroleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT yoshionakajima roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT yutakanakamura roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT watarushigeeda roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT makototomoyasu roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT hiroyukideguchi roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT tatsuotanita roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells AT koheiyamauchi roleoftumornecrosisfactoraandinterferonginregulatingangiomotinlikeprotein1expressioninlungmicrovascularendothelialcells |
_version_ |
1725657974281601024 |