Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells

Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little i...

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Main Authors: Frida Berlin, Sofia Mogren, Camilla Ly, Sangeetha Ramu, Morten Hvidtfeldt, Lena Uller, Celeste Porsbjerg, Cecilia K. Andersson
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/12/10/1439
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author Frida Berlin
Sofia Mogren
Camilla Ly
Sangeetha Ramu
Morten Hvidtfeldt
Lena Uller
Celeste Porsbjerg
Cecilia K. Andersson
author_facet Frida Berlin
Sofia Mogren
Camilla Ly
Sangeetha Ramu
Morten Hvidtfeldt
Lena Uller
Celeste Porsbjerg
Cecilia K. Andersson
author_sort Frida Berlin
collection DOAJ
description Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth–death regulation.
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spelling doaj.art-446aa61587d04f7eb9e80020ecb71d2f2023-11-18T00:53:38ZengMDPI AGCells2073-44092023-05-011210143910.3390/cells12101439Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial CellsFrida Berlin0Sofia Mogren1Camilla Ly2Sangeetha Ramu3Morten Hvidtfeldt4Lena Uller5Celeste Porsbjerg6Cecilia K. Andersson7Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Lund University, 22184 Lund, SwedenDepartment of Experimental Medical Science, Lund University, 22184 Lund, SwedenDepartment of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, DenmarkDepartment of Experimental Medical Science, Lund University, 22184 Lund, SwedenDepartment of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, DenmarkDepartment of Experimental Medical Science, Lund University, 22184 Lund, SwedenBronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth–death regulation.https://www.mdpi.com/2073-4409/12/10/1439mast cellproteasestryptasebronchial epitheliumalveolar epitheliumgrowth factors
spellingShingle Frida Berlin
Sofia Mogren
Camilla Ly
Sangeetha Ramu
Morten Hvidtfeldt
Lena Uller
Celeste Porsbjerg
Cecilia K. Andersson
Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
Cells
mast cell
proteases
tryptase
bronchial epithelium
alveolar epithelium
growth factors
title Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
title_full Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
title_fullStr Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
title_full_unstemmed Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
title_short Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells
title_sort mast cell tryptase promotes airway remodeling by inducing anti apoptotic and cell growth properties in human alveolar and bronchial epithelial cells
topic mast cell
proteases
tryptase
bronchial epithelium
alveolar epithelium
growth factors
url https://www.mdpi.com/2073-4409/12/10/1439
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