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Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface

The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface li...

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Detalles Bibliográficos
Autores principales: Stanke, Frauke, Janciauskiene, Sabina, Tamm, Stephanie, Wrenger, Sabine, Raddatz, Ellen Luise, Jonigk, Danny, Braubach, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125203/
https://www.ncbi.nlm.nih.gov/pubmed/33946490
http://dx.doi.org/10.3390/molecules26092639
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author Stanke, Frauke
Janciauskiene, Sabina
Tamm, Stephanie
Wrenger, Sabine
Raddatz, Ellen Luise
Jonigk, Danny
Braubach, Peter
author_facet Stanke, Frauke
Janciauskiene, Sabina
Tamm, Stephanie
Wrenger, Sabine
Raddatz, Ellen Luise
Jonigk, Danny
Braubach, Peter
author_sort Stanke, Frauke
collection PubMed
description The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR.
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spelling pubmed-81252032021-05-17 Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface Stanke, Frauke Janciauskiene, Sabina Tamm, Stephanie Wrenger, Sabine Raddatz, Ellen Luise Jonigk, Danny Braubach, Peter Molecules Article The cystic fibrosis transmembrane conductance regulator (CFTR) gene is influenced by the fundamental cellular processes like epithelial differentiation/polarization, regeneration and epithelial–mesenchymal transition. Defects in CFTR protein levels and/or function lead to decreased airway surface liquid layer facilitating microbial colonization and inflammation. The SERPINA1 gene, encoding alpha1-antitrypsin (AAT) protein, is one of the genes implicated in CF, however it remains unknown whether AAT has any influence on CFTR levels. In this study we assessed CFTR protein levels in primary human lung epithelial cells grown at the air-liquid-interface (ALI) alone or pre-incubated with AAT by Western blots and immunohistochemistry. Histological analysis of ALI inserts revealed CFTR- and AAT-positive cells but no AAT-CFTR co-localization. When 0.5 mg/mL of AAT was added to apical or basolateral compartments of pro-inflammatory activated ALI cultures, CFTR levels increased relative to activated ALIs. This finding suggests that AAT is CFTR-modulating protein, albeit its effects may depend on the concentration and the route of administration. Human lung epithelial ALI cultures provide a useful tool for studies in detail how AAT or other pharmaceuticals affect the levels and activity of CFTR. MDPI 2021-04-30 /pmc/articles/PMC8125203/ /pubmed/33946490 http://dx.doi.org/10.3390/molecules26092639 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Stanke, Frauke
Janciauskiene, Sabina
Tamm, Stephanie
Wrenger, Sabine
Raddatz, Ellen Luise
Jonigk, Danny
Braubach, Peter
Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title_full Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title_fullStr Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title_full_unstemmed Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title_short Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface
title_sort effect of alpha-1 antitrypsin on cftr levels in primary human airway epithelial cells grown at the air-liquid-interface
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125203/
https://www.ncbi.nlm.nih.gov/pubmed/33946490
http://dx.doi.org/10.3390/molecules26092639
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