Abstract
Introduction: Epithelial remodelling and dysfunction are characteristics for asthmatic disease. In asthma, mast cells (MCs) infiltrate the epithelium and alveolar parenchyma. However, the MC-epithelium crosstalk is not known. We aim to study if MC proteases tryptase and chymase induce bronchial and alveolar remodelling in a viral environment.
Methods: Human bronchial and alveolar epithelial cells were treated with MC tryptase and/or chymase and co-stimulated with toll-like receptor agonists to mimic a pro-inflammatory/viral setting. Cell growth were assessed using holographic live cell imaging and a profiler gene array associated with cell survival. Data was confirmed with qPCR, western blot and immunocytochemistry. The epithelial release of vascular epithelial growth factor (VEGF) and fibroblastic growth factors (FGF) was analysed.
Results: Tryptase enhanced cell growth and release of VEGF and FGF in bronchial and alveolar cells when compared to non-stimulated cells, both in normal and pro-inflammatory/viral condition. Anti-apoptotic proteins BIRC3 and BFL-1 was increased in tryptase treated cells, both at gene and protein level. No alterations was found in chymase treated cells compared to non-stimulated cells.
Conclusion: We show that MC tryptase, but not chymase, increases cell growth, anti-apoptotic gene and protein expression as well as release of growth factors in bronchial and alveolar epithelial cells. These effects remained elevated in a pro-inflammatory and viral milieu. Thus, our data implies that MC release of tryptase may play a critical role in airway epithelial and alveolar homeostasis by disturbing cell growth-death regulations.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 93.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022