A Senescence Bystander Effect in Human Lung Fibroblasts
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of...
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doaj-9b887b3e6a684a2cbaf59851201b3ebd2021-09-25T23:46:32ZengMDPI AGBiomedicines2227-90592021-09-0191162116210.3390/biomedicines9091162A Senescence Bystander Effect in Human Lung FibroblastsDavid W. Waters0Michael Schuliga1Prabuddha S. Pathinayake2Lan Wei3Hui-Ying Tan4Kaj E. C. Blokland5Jade Jaffar6Glen P. Westall7Janette K. Burgess8Cecilia M. Prêle9Steven E. Mutsaers10Christopher L. Grainge11Darryl A. Knight12School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaAllergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, VIC 3004, AustraliaAllergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, VIC 3004, AustraliaUniversity Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, 9713 GZ Groningen, The NetherlandsCentre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, University of Western Australia, Nedlands, WA 6009, AustraliaCentre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, University of Western Australia, Nedlands, WA 6009, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, AustraliaIdiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of IPF patients compared with age-matched controls. The cause of this abnormal accumulation of senescent cells is unknown but evidence suggests that, once established, senescence can be transferred from senescent to non-senescent cells. In this study, we investigated whether senescent human lung fibroblasts (LFs) and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in “naïve” non-senescent LFs in vitro. Primary cultures of LFs from adult control donors (Ctrl-LFs) with a low baseline of senescence were exposed to conditioned medium (CM) from: (i) Ctrl-LFs induced to become senescent using H<sub>2</sub>O<sub>2</sub> or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients.https://www.mdpi.com/2227-9059/9/9/1162collagenidiopathic pulmonary fibrosis (IPF)lung fibroblastssenescence |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David W. Waters Michael Schuliga Prabuddha S. Pathinayake Lan Wei Hui-Ying Tan Kaj E. C. Blokland Jade Jaffar Glen P. Westall Janette K. Burgess Cecilia M. Prêle Steven E. Mutsaers Christopher L. Grainge Darryl A. Knight |
spellingShingle |
David W. Waters Michael Schuliga Prabuddha S. Pathinayake Lan Wei Hui-Ying Tan Kaj E. C. Blokland Jade Jaffar Glen P. Westall Janette K. Burgess Cecilia M. Prêle Steven E. Mutsaers Christopher L. Grainge Darryl A. Knight A Senescence Bystander Effect in Human Lung Fibroblasts Biomedicines collagen idiopathic pulmonary fibrosis (IPF) lung fibroblasts senescence |
author_facet |
David W. Waters Michael Schuliga Prabuddha S. Pathinayake Lan Wei Hui-Ying Tan Kaj E. C. Blokland Jade Jaffar Glen P. Westall Janette K. Burgess Cecilia M. Prêle Steven E. Mutsaers Christopher L. Grainge Darryl A. Knight |
author_sort |
David W. Waters |
title |
A Senescence Bystander Effect in Human Lung Fibroblasts |
title_short |
A Senescence Bystander Effect in Human Lung Fibroblasts |
title_full |
A Senescence Bystander Effect in Human Lung Fibroblasts |
title_fullStr |
A Senescence Bystander Effect in Human Lung Fibroblasts |
title_full_unstemmed |
A Senescence Bystander Effect in Human Lung Fibroblasts |
title_sort |
senescence bystander effect in human lung fibroblasts |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2021-09-01 |
description |
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of IPF patients compared with age-matched controls. The cause of this abnormal accumulation of senescent cells is unknown but evidence suggests that, once established, senescence can be transferred from senescent to non-senescent cells. In this study, we investigated whether senescent human lung fibroblasts (LFs) and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in “naïve” non-senescent LFs in vitro. Primary cultures of LFs from adult control donors (Ctrl-LFs) with a low baseline of senescence were exposed to conditioned medium (CM) from: (i) Ctrl-LFs induced to become senescent using H<sub>2</sub>O<sub>2</sub> or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients. |
topic |
collagen idiopathic pulmonary fibrosis (IPF) lung fibroblasts senescence |
url |
https://www.mdpi.com/2227-9059/9/9/1162 |
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