Abstract

Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

Details

Title
Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors
Author
Burgess, J K 1   VIAFID ORCID Logo  ; Ketheson, A 2 ; Faiz, A 3 ; Limbert Rempel, K A 4 ; Oliver, B G 5 ; Ward, J P T 6 ; Halayko, A J 4 

1  University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, KOLFF Institute, Groningen, The Netherlands; Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; Discipline of Pharmacology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia 
2  Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; Discipline of Pharmacology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia 
3  University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pulmonology, GRIAC (Groningen Research Institute for Asthma and COPD), Groningen, The Netherlands 
4  University of Manitoba and Children’s Hospital Research Institute of Manitoba, Winnipeg, Canada 
5  Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia; School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, NSW, Australia 
6  Kings College London, London, UK 
Pages
1-12
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-18429-0
ProQuest document ID
1988111940
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.