Abstract
Volatile organic compounds (VOCs) have shown promise as potential biomarkers in idiopathic pulmonary fibrosis. Measuring VOCs in the headspace of in vitro models of lung fibrosis may offer a method of determining the origin of those detected in exhaled breath. The aim of this study was to determine the VOCs associated with two lung cell lines (A549 and MRC-5 cells) and changes associated with stimulation of cells with the pro-fibrotic cytokine, transforming growth factor (TGF)-β1. A dynamic headspace sampling method was used to sample the headspace of A549 cells and MRC-5 cells. These were compared to media control samples and to each other to identify VOCs which discriminated between cell lines. Cells were then stimulated with the TGF-β1 and samples were compared between stimulated and unstimulated cells. Samples were analysed using thermal desorption-gas chromatography-mass spectrometry and supervised analysis was performed using sparse partial least squares-discriminant analysis (sPLS-DA). Supervised analysis revealed differential VOC profiles unique to each of the cell lines and from the media control samples. Significant changes in VOC profiles were induced by stimulation of cell lines with TGF-β1. In particular, several terpenoids (isopinocarveol, sativene and 3-carene) were increased in stimulated cells compared to unstimulated cells. VOC profiles differ between lung cell lines and alter in response to pro-fibrotic stimulation. Increased abundance of terpenoids in the headspace of stimulated cells may reflect TGF-β1 cell signalling activity and metabolic reprogramming. This may offer a potential biomarker target in exhaled breath in IPF.
| Original language | English |
|---|---|
| Article number | 046012 |
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | Journal of Breath Research |
| Volume | 17 |
| Issue number | 4 |
| Early online date | 7 Sept 2023 |
| DOIs | |
| Publication status | Published (in print/issue) - 1 Oct 2023 |
Bibliographical note
Funding Information:This study was supported by a grant from the North West Lung Centre Charity. W A and S J F are supported by the NIHR-Manchester Biomedical Research Centre. JFB is a MRC transition support fellow (MR/T032529/1) and is supported by grants from Asthma+Lung UK and also the NIHR-Manchester Biomedical Research Centre.
Publisher Copyright:
© 2023 The Author(s). Published by IOP Publishing Ltd.
Keywords
- cell culture models
- volatile organic compounds
- idiopathic pulmonary fibrosis
- headspace
